Journal articles on the topic 'Osteogenic therapies'
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1
Helm, Gregory A., Hayan Dayoub, and John A. Jane. "Gene-based therapies for the induction of spinal fusion." Neurosurgical Focus 10, no. 4 (April 2001): 1–5. http://dx.doi.org/10.3171/foc.2001.10.4.6.
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Numerous mesenchymal growth factors with osteogenic properties have now been identified. Although many of these proteins can induce bone formation when delivered on a carrier matrix, these approaches have not been fully developed in the laboratory or clinic. The expression of osteogenic proteins via direct or ex vivo gene therapy techniques is also compelling because high-level, long-term gene expression can now be achieved using novel viral and nonviral vectors. In this brief review the authors will highlight recent advances in genetic therapies for the induction of osteogenesis, as well as their potential use for the promotion of spinal arthrodesis.
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Martin-Iglesias, Sara, Lara Milian, María Sancho-Tello, Rubén Salvador-Clavell, José Javier Martín de Llano, Carmen Carda, and Manuel Mata. "BMP-2 Enhances Osteogenic Differentiation of Human Adipose-Derived and Dental Pulp Stem Cells in 2D and 3D In Vitro Models." Stem Cells International 2022 (March 4, 2022): 1–15. http://dx.doi.org/10.1155/2022/4910399.
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Bone tissue provides support and protection to different organs and tissues. Aging and different diseases can cause a decrease in the rate of bone regeneration or incomplete healing; thus, tissue-engineered substitutes can be an acceptable alternative to traditional therapies. In the present work, we have developed an in vitro osteogenic differentiation model based on mesenchymal stem cells (MSCs), to first analyse the influence of the culture media and the origin of the cells on the efficiency of this process and secondly to extrapolate it to a 3D environment to evaluate its possible application in bone regeneration therapies. Two osteogenic culture media were used (one commercial from Stemcell Technologies and a second supplemented with dexamethasone, ascorbic acid, glycerol-2-phosphate, and BMP-2), with human cells of a mesenchymal phenotype from two different origins: adipose tissue (hADSCs) and dental pulp (hDPSCs). The expression of osteogenic markers in 2D cultures was evaluated in several culture periods by means of the immunofluorescence technique and real-time gene expression analysis, taking as reference MG-63 cells of osteogenic origin. The same strategy was extrapolated to a 3D environment of polylactic acid (PLA), with a 3% alginate hydrogel. The expression of osteogenic markers was detected in both hADSCs and hDPSCs, cultured in either 2D or 3D environments. However, the osteogenic differentiation of MSCs was obtained based on the culture medium and the cell origin used, since higher osteogenic marker levels were found when hADSCs were cultured with medium supplemented with BMP-2. Furthermore, the 3D culture used was suitable for cell survival and osteogenic induction.
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Zaidi, M., N. Zaidi, and L. Sun. "EP receptor agonists and other osteogenic therapies for bone repair." Drugs of the Future 32, no. 9 (2007): 833. http://dx.doi.org/10.1358/dof.2007.032.09.1124489.
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Manochantr, Sirikul, Kulisara Marupanthorn, Chairat Tantrawatpan, Pakpoom Kheolamai, Duangrat Tantikanlayaporn, and Prakasit Sanguanjit. "The Effects of BMP-2, miR-31, miR-106a, and miR-148a on Osteogenic Differentiation of MSCs Derived from Amnion in Comparison with MSCs Derived from the Bone Marrow." Stem Cells International 2017 (2017): 1–14. http://dx.doi.org/10.1155/2017/7257628.
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Mesenchymal stromal cells (MSCs) offering valuable anticipations for the treatment of degenerative diseases. They can be found in many tissues including amnion. MSCs from amnion (AM-MSCs) can differentiate into osteoblast similar to that of bone marrow-derived MSCs (BM-MSCs). However, the ability is not much efficient compared to BM-MSCs. This study aimed to examine the effects of BMP-2 and miRNAs on osteogenic differentiation of AM-MSCs compared to those of BM-MSCs. The osteogenic differentiation capacity after miRNA treatment was assessed by ALP expression, ALP activity, and osteogenic marker gene expression. The results showed that the osteogenic differentiation capacity increased after BMP-2 treatment both in AM-MSCs and BM-MSCs. MiR-31, miR-106a, and miR-148a were downregulated during the osteogenic differentiation. After transfection with anti-miRNAs, ALP activity and osteogenic genes were increased over the time of differentiation. The data lead to the potential for using AM-MSCs as an alternative source for bone regeneration. Moreover, the information of miRNA expression and function during osteogenic differentiation may be useful for the development of new therapeutics or enhanced an in vitro culture technique required for stem cell-based therapies in the bone regeneration.
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Herten, M., M. Sager, L. Benga, J. C. Fischer, M. Jäger, M. Betsch, M. Wild, M. Hakimi, P. Jungbluth, and J. P. Grassmann. "Bone marrow concentrate for autologous transplantation in minipigs." Veterinary and Comparative Orthopaedics and Traumatology 26, no. 01 (2013): 34–41. http://dx.doi.org/10.3415/vcot-11-11-0165.
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SummaryAutologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential.Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells.The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model.This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.
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Favi, Pelagie, Madhu Dhar, Nancy Neilsen, and Roberto Benson. "Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells on Biodegradable Calcium-deficient Hydroxyapatite Tubular Bacterial Cellulose Composites." MRS Proceedings 1621 (2014): 71–79. http://dx.doi.org/10.1557/opl.2014.287.
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ABSTRACTAdvanced biomaterials that mimic the structure and function of native tissues and permit stem cells to adhere and differentiate is of paramount importance in the development of stem cell therapies for bone defects. Successful bone repair approaches may include an osteoconductive scaffold that permits excellent cell adhesion and proliferation, and cells with an osteogenic potential. The objective of this study was to evaluate the cell proliferation, viability and osteocyte differentiation of equine-derived bone marrow mesenchymal stem cells (EqMSCs) when seeded onto biocompatible and biodegradable calcium-deficient hydroxyapatite (CdHA) tubular-shaped bacterial cellulose scaffolds (BC-TS) of various sizes. The biocompatible gel-like BC-TS was synthesized using the bacterium Gluconacetobacter sucrofermentans under static culture in oxygen-permeable silicone tubes. The BC-TS scaffolds were modified using a periodate oxidation to yield biodegradable scaffolds. Additionally, CdHA was deposited in the scaffolds to mimic native bone tissues. The morphological properties of the resulting BC-TS and its composites were characterized using scanning electron microscopy. The ability of the BC-TS and its composites to support and maintain EqMSCs growth, proliferation and osteogenic differentiation in vitro was also assessed. BC-TS and its composites exhibited aligned nanofibril structures. MTS assay demonstrated increasing proliferation and viability with time (days 1, 2 and 3). Cell-scaffold constructs were cultured for 8 days under osteogenic conditions and the resulting osteocytes were positive for alizarin red. In summary, biocompatible and biodegradable CdHA BC-TS composites support the proliferation, viability and osteogenic differentiation of EqMSCs cultured onto its surface in vitro, allowing for future potential use for tissue engineering therapies.
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Littman, Neil, and Arie Abo. "Proceedings: Using Stem Cell Therapies to Reestablish Osteogenic Capability for Bone Regeneration." STEM CELLS Translational Medicine 4, no. 11 (October 19, 2015): 1247–50. http://dx.doi.org/10.5966/sctm.2015-0202.
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Huang, Yueyue, Shuang Wu, Yi Zhou, Yue Zhou, Xiaomei Xu, Dongchuan Zuo, Xiaoping Yuan, and Jin Zeng. "The Effects of Extracts from "Red Complex" Pathogens on Human Dental Follicle Cells." Journal of Biomaterials and Tissue Engineering 10, no. 8 (August 1, 2020): 1128–34. http://dx.doi.org/10.1166/jbt.2020.2370.
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Dental follicle cells could be a natural source of cells for regeneration therapies in periodontitis. The "red complex", which include Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, is strongly associated with periodontitis. However, the effects of "red complex" on dental follicle cells remains largely unknown. In this study, we evaluated the effects of bacterial extracts obtained from Porphyromonas gingivalis and from "red complex" (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia in co-culture) on proliferation, migration and osteogenic differentiation of human dental follicle cells. Our data showed that bacterial extracts promoted cell proliferation and migration, decreased the alkaline phosphatase activity, osteogenic genes expression and formation of mineral deposits. Noticeably, compared with the inhibitory effects induced by bacterial extracts from Porphyromonas gingivalis on osteogenic differentiation of human dental follicle cells, the inhibitory effects induced by bacterial extracts from "red complex" were more significant. In conclusion, the extracts from "red complex" pathogens inhibited osteogenic differentiation capacity of human dental follicle cells, and this provides a theoretical basis for the clinical application of stem cell therapy in periodontal tissue engineering.
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Pieles, Oliver, Marcus Höring, Sadiyeh Adel, Torsten E. Reichert, Gerhard Liebisch, and Christian Morsczeck. "Energy Metabolism and Lipidome Are Highly Regulated during Osteogenic Differentiation of Dental Follicle Cells." Stem Cells International 2022 (July 16, 2022): 1–20. http://dx.doi.org/10.1155/2022/3674931.
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Dental follicle cells (DFCs) are stem/progenitor cells of the periodontium and give rise to alveolar osteoblasts. However, understanding of the molecular mechanisms of osteogenic differentiation, which is required for cell-based therapies, is delimited. This study is aimed at analyzing the energy metabolism during the osteogenic differentiation of DFCs. Human DFCs were cultured, and osteogenic differentiation was induced by either dexamethasone or bone morphogenetic protein 2 (BMP2). Previous microarray data were reanalyzed to examine pathways that are regulated after osteogenic induction. Expression and activity of metabolic markers were evaluated by western blot analysis and specific assays, relative amount of mitochondrial DNA was measured by real-time quantitative polymerase chain reaction, the oxidative state of cells was determined by a glutathione assay, and the lipidome of cells was analyzed via mass spectrometry (MS). Moreover, osteogenic markers were analyzed after the inhibition of fatty acid synthesis by 5-(tetradecyloxy)-2-furoic acid or C75. Pathway enrichment analysis of microarray data revealed that carbon metabolism was amongst the top regulated pathways after osteogenic induction in DFCs. Further analysis showed that enzymes involved in glycolysis, citric acid cycle, mitochondrial activity, and lipid metabolism are differentially expressed during differentiation, with most markers upregulated and more markedly after induction with dexamethasone compared to BMP2. Moreover, the cellular state was more oxidized, and mitochondrial DNA was distinctly upregulated during the second half of differentiation. Besides, MS of the lipidome revealed higher lipid concentrations after osteogenic induction, with a preference for species with lower numbers of C-atoms and double bonds, which indicates a de novo synthesis of lipids. Concordantly, inhibition of fatty acid synthesis impeded the osteogenic differentiation of DFCs. This study demonstrates that energy metabolism is highly regulated during osteogenic differentiation of DFCs including changes in the lipidome suggesting enhanced de novo synthesis of lipids, which are required for the differentiation process.
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Gao, Jianliang, Shouyu Xiang, Xiao Wei, Ram Ishwar Yadav, Menghu Han, Weihao Zheng, Lili Zhao, Yichuan Shi, and Yanming Cao. "Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/β-Catenin Signaling Pathway." BioMed Research International 2021 (January 22, 2021): 1–10. http://dx.doi.org/10.1155/2021/6666836.
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Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/β-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene (SOST) overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, β-catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/β-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP.
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Gromolak, Sandra, Agnieszka Krawczenko, Agnieszka Antończyk, Krzysztof Buczak, Zdzisław Kiełbowicz, and Aleksandra Klimczak. "Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2." International Journal of Molecular Sciences 21, no. 24 (December 20, 2020): 9726. http://dx.doi.org/10.3390/ijms21249726.
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Cell-based therapies using mesenchymal stem cells (MSCs) are a promising tool in bone tissue engineering. Bone regeneration with MSCs involves a series of molecular processes leading to the activation of the osteoinductive cascade supported by bioactive factors, including fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2). In this study, we examined the biological characteristics and osteogenic differentiation potential of sheep bone marrow MSCs (BM-MSCs) treated with 20 ng/mL of FGF-2 and 100 ng/mL BMP-2 in vitro. The biological properties of osteogenic-induced BM-MSCs were investigated by assessing their morphology, proliferation, phenotype, and cytokine secretory profile. The osteogenic differentiation was characterized by Alizarin Red S staining, immunofluorescent staining of osteocalcin and collagen type I, and expression levels of genetic markers of osteogenesis. The results demonstrated that BM-MSCs treated with FGF-2 and BMP-2 maintained their primary MSC properties and improved their osteogenic differentiation capacity, as confirmed by increased expression of osteocalcin and collagen type I and upregulation of osteogenic-related gene markers BMP-2, Runx2, osterix, collagen type I, osteocalcin, and osteopontin. Furthermore, sheep BM-MSCs produced a variety of bioactive factors involved in osteogenesis, and supplementation of the culture medium with FGF-2 and BMP-2 affected the secretome profile of the cells. The results suggest that sheep osteogenic-induced BM-MSCs may be used as a cellular therapy to study bone repair in the preclinical large animal model.
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Bicer, Mesude, Jonathan Sheard, Donata Iandolo, Samuel Y. Boateng, Graeme S. Cottrell, and Darius Widera. "Electrical Stimulation of Adipose-Derived Stem Cells in 3D Nanofibrillar Cellulose Increases Their Osteogenic Potential." Biomolecules 10, no. 12 (December 18, 2020): 1696. http://dx.doi.org/10.3390/biom10121696.
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Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of viable, autologous bone grafts is limited making alternative cell-based strategies a promising therapeutic alternative. Adipose-derived stem cells (ASCs) are a readily available population of mesenchymal stem/stromal cells (MSCs) that can be isolated within minimally invasive surgery. This ease of availability and their ability to undergo osteogenic differentiation makes ASCs promising candidates for cell-based therapies for bone fractures. Recent studies have suggested that both exposure to electrical fields and cultivation in 3D can positively affect osteogenic potential of MSCs. To elucidate the osteoinductive potential of a combination of these biophysical cues on ASCs, cells were embedded within anionic nanofibrillar cellulose (aNFC) hydrogels and exposed to electrical stimulation (ES) for up to 21 days. ES was applied to ASCs in 2D and 3D at a voltage of 0.1 V/cm with a duration of 0.04 ms, and a frequency of 10 Hz for 30 min per day. Exposure of ASCs to ES in 3D resulted in high alkaline phosphatase (ALP) activity and in an increased mineralisation evidenced by Alizarin Red S staining. Moreover, ES in 3D aNFC led to an increased expression of the osteogenic markers osteopontin and osteocalcin and a rearrangement and alignment of the actin cytoskeleton. Taken together, our data suggest that a combination of ES with 3D cell culture can increase the osteogenic potential of ASCs. Thus, exposure of ASCs to these biophysical cues might improve the clinical outcomes of regenerative therapies in treatment of osteoporotic fractures.
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Morsczeck, Christian. "Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells." International Journal of Molecular Sciences 23, no. 11 (May 25, 2022): 5945. http://dx.doi.org/10.3390/ijms23115945.
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Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if innovative regenerative therapies in medicine are often considered the main research area for dental stem cells, these cells are also very useful in basic research and here, for example, for the elucidation of molecular processes in the differentiation into mineralizing cells. This article summarizes the molecular mechanisms driving osteogenic differentiation of DFCs. The positive feedback loop of bone morphogenetic protein (BMP) 2 and homeobox protein DLX3 and a signaling pathway associated with protein kinase B (AKT) and protein kinase C (PKC) are presented and further insights related to other signaling pathways such as the WNT signaling pathway are explained. Subsequently, some works are presented that have investigated epigenetic modifications and non-coding ncRNAs and their connection with the osteogenic differentiation of DFCs. In addition, studies are presented that have shown the influence of extracellular matrix molecules or fundamental biological processes such as cellular senescence on osteogenic differentiation. The putative role of factors associated with inflammatory processes, such as interleukin 8, in osteogenic differentiation is also briefly discussed. This article summarizes the most important insights into the mechanisms of osteogenic differentiation in DFCs and is intended to be a small help in the direction of new research projects in this area.
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Zhao, Dan, Wen Kang, Yiwen Wang, Jiuyu Ge, Jianfeng Huang, Jie Yang, Weidong Yang, Xuna Tang, and Sijing Xie. "SIRT1 Promotes Osteogenic Differentiation in Human Dental Pulp Stem Cells through Counteracting the Activation of STAT3." Coatings 11, no. 11 (November 3, 2021): 1353. http://dx.doi.org/10.3390/coatings11111353.
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Human dental pulp stem cells (hDPSCs), which are characterized by self-renewal capacity and the ability of multilineage differentiation, have gained increased attention in regenerative medicine recently. Histone acetylation modulator proteins (HAMPs) are a protein family that mediates the modification and identification of histone acetylation and participates in various critical cellular processes. Here, we comprehensively surveyed the expression profile of HAMPs during osteoblast differentiation of hDPSCs and found that the HDAC class III pathway was upregulated, whereas the signal transducer and activator of transcription 3 (STAT3) signaling was downregulated during osteogenesis. Further laboratory research demonstrated that Sirtuin-1 (SIRT1), a class III HDAC, was upregulated and STAT3 activation was downregulated during osteogenic differentiation. SIRT1 counteracted the activation of STAT3 to promote osteogenic differentiation of hDPSCs at 7 and 21 days in both Western blot assay and chemical staining, which highlights the promising utility of SIRT1 activators in hDPSCs-based therapies for bone augmentation strategies and provides clinical insights that may lead to the development of osteogenic agents.
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Liang, Changxiang, Guoyan Liang, Xiaoqing Zheng, Yongxiong Huang, Shuaihao Huang, and Dong Yin. "RSP5 Positively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells by Activating the K63-Linked Ubiquitination of Akt." Stem Cells International 2020 (April 6, 2020): 1–13. http://dx.doi.org/10.1155/2020/7073805.
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Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.
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Rovai, Emanuel Silva, Lucas Macedo Batitucci Ambrósio, Bruno Nunes de França, Letícia Rodrigues de Oliveira, Letícia Miquelitto Gasparoni, Carla Renata Sipert, and Marinella Holzhausen. "Protease-Activated Receptor Type 1 Activation Enhances Osteogenic Activity in Human Periodontal Ligament Stem Cells." Stem Cells International 2019 (June 2, 2019): 1–11. http://dx.doi.org/10.1155/2019/6857386.
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Protease-activated receptor 1 (PAR1) has been associated to tissue repair and bone healing. The aim of the present study was to evaluate the effect of PAR1 activation on the osteogenic activity of human periodontal ligament stem cells (PDLSCs). PDLSCs were cultured in the presence of PAR1-selective agonist peptide (100 nM), thrombin (0.1 U/mL), or PAR1 antagonist peptide (100 nM). Calcium deposits, calcium concentration (supernatant), alkaline phosphatase activity (ALP), cell proliferation, and gene (qPCR) and protein expression (ELISA assay) of osteogenic factors were assessed at 2, 7, and 14 days. PAR1 activation led to increased calcium deposits (p<0.05), calcium concentration (p<0.05), ALP activity (p<0.05), and cell proliferation (p<0.05). Further, PAR1 activation may increase gene and protein expression of Runx2 (p<0.05) and OPG (p<0.05). In conclusion, PAR1 activation increases osteogenic activity of PDLSCs, providing a possible new strategy for periodontal regenerative therapies.
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Khayat, Ghazaleh, Derek H. Rosenzweig, Zohreh Khavandgar, Jingjing Li, Monzur Murshed, and Thomas M. Quinn. "Low-Frequency Mechanical Stimulation Modulates Osteogenic Differentiation of C2C12 Cells." ISRN Stem Cells 2013 (February 19, 2013): 1–9. http://dx.doi.org/10.1155/2013/138704.
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Mechanical stimulation influences stem cell differentiation and may therefore provide improved lineage specification control for clinical applications. Low-frequency oscillatory mechanical stimulation (0.01 Hz) has recently been shown to suppress adipogenic differentiation of mesenchymal stem cells, indicating that the range of effective stimulation frequencies is not limited to those associated with locomotion, circulation, and respiration. We hypothesized that low-frequency mechanical stimulation (0.01 Hz) can also promote osteogenic cell differentiation of myoblastic C2C12 cells in combination with BMP-2. Results indicate that low-frequency mechanical stimulation can significantly enhance osteogenic gene expression, provided that differentiation is initiated by a priming period involving BMP-2 alone. Subsequent application of low-frequency mechanical stimulation appears to act synergistically with continued BMP-2 exposure to promote osteogenic differentiation of C2C12 cells and can even partially compensate for the removal of BMP-2. These effects may be mediated by the ERK and Wnt signalling pathways. Osteogenic induction of C2C12 cells by low-frequency mechanical stimulation is therefore critically dependent upon previous exposure to growth factors, and the timing of superimposed BMP-2 and mechanical stimuli can sensitively influence osteogenesis. These insights may provide a technically simple means for control of stem cell differentiation in cell-based therapies, particularly for the enhancement of differentiation toward desired lineages.
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Waddell, Shona J., María C. de Andrés, Penelope M. Tsimbouri, Enateri V. Alakpa, Maggie Cusack, Matthew J. Dalby, and Richard OC Oreffo. "Biomimetic oyster shell–replicated topography alters the behaviour of human skeletal stem cells." Journal of Tissue Engineering 9 (January 2018): 204173141879400. http://dx.doi.org/10.1177/2041731418794007.
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The regenerative potential of skeletal stem cells provides an attractive prospect to generate bone tissue needed for musculoskeletal reparation. A central issue remains efficacious, controlled cell differentiation strategies to aid progression of cell therapies to the clinic. The nacre surface from Pinctada maxima shells is known to enhance bone formation. However, to date, there is a paucity of information on the role of the topography of P. maxima surfaces, nacre and prism. To investigate this, nacre and prism topographical features were replicated onto polycaprolactone and skeletal stem cell behaviour on the surfaces studied. Skeletal stem cells on nacre surfaces exhibited an increase in cell area, increase in expression of osteogenic markers ALP ( p < 0.05) and OCN ( p < 0.01) and increased metabolite intensity ( p < 0.05), indicating a role of nacre surface to induce osteogenic differentiation, while on prism surfaces, skeletal stem cells did not show alterations in cell area or osteogenic marker expression and a decrease in metabolite intensity ( p < 0.05), demonstrating a distinct role for the prism surface, with the potential to maintain the skeletal stem cell phenotype.
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Li, Dijie, Ye Tian, Chong Yin, Ying Huai, Yipu Zhao, Peihong Su, Xue Wang, et al. "Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis." International Journal of Molecular Sciences 20, no. 24 (December 10, 2019): 6229. http://dx.doi.org/10.3390/ijms20246229.
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Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory. In this study we identify a novel long noncoding RNA AK045490 which is correlated with osteogenic differentiation and enriched in skeletal tissues of mice. In vitro analysis of bone-derived mesenchymal stem cells (BMSCs) showed that AK045490 inhibited osteoblast differentiation. In vivo inhibition of AK045490 by its small interfering RNA rescued bone formation in ovariectomized osteoporosis mice model. Mechanistically, AK045490 inhibited the nuclear translocation of β-catenin and downregulated the expression of TCF1, LEF1, and Runx2. The results suggest that Lnc-AK045490 suppresses β-catenin/TCF1/Runx2 signaling and inhibits osteoblast differentiation and bone formation, providing a novel mechanism of osteogenic differentiation and a potential drug target for osteoporosis.
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Li, Chunrong, Xin Li, Xian Wang, Pei Miao, Jia Liu, Cuixia Li, Doudou Li, Weiwei Zhou, Zuolin Jin, and Meng Cao. "Periostin Mediates Oestrogen-Induced Osteogenic Differentiation of Bone Marrow Stromal Cells in Ovariectomised Rats." BioMed Research International 2020 (April 30, 2020): 1–10. http://dx.doi.org/10.1155/2020/9405909.
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Osteoporosis is a metabolic disease that results in the progressive loss of bone mass, which, in postmenopausal women, is related to oestrogen deficiency. Periostin (POSTN) plays a key role in the early stages of bone formation. However, whether POSTN participates in oestradiol regulation of osteogenic differentiation of bone marrow stromal cells (BMSCs) from ovariectomised (OVX) rats remains unclear. In vivo, using microcomputed tomography (micro-CT), immunohistochemistry, and dynamic analysis of femurs, we found that 17β-E2 promotes bone formation and POSTN expression at the endosteal surface. In vitro, 17β-E2 upregulated POSTN expression in OVX-BMSCs. POSTN overexpression activated the Wnt/β-catenin signalling pathway and enhanced osteogenic differentiation of OVX-BMSCs. Furthermore, knockdown of Postn blocks the involvement of 17β-E2 in the osteogenic differentiation of OVX-BMSCs. Collectively, our study indicated the role of POSTN in the osteogenesis and stemness of OVX-BMSCs and proves that 17β-E2 reduces osteoporosis and promotes osteogenesis through the POSTN-Wnt/β-catenin pathway. POSTN could, therefore, be a novel target gene for anti-osteoporosis therapies.
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Weber, Marbod, Felix Umrath, Heidrun Steinle, Lukas-Frank Schmitt, Lin Tzu Yu, Christian Schlensak, Hans-Peter Wendel, Siegmar Reinert, Dorothea Alexander, and Meltem Avci-Adali. "Influence of Human Jaw Periosteal Cells Seeded β-Tricalcium Phosphate Scaffolds on Blood Coagulation." International Journal of Molecular Sciences 22, no. 18 (September 14, 2021): 9942. http://dx.doi.org/10.3390/ijms22189942.
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Tissue engineering offers auspicious opportunities in oral and maxillofacial surgery to heal bone defects. For this purpose, the combination of cells with stability-providing scaffolds is required. Jaw periosteal cells (JPCs) are well suited for regenerative therapies, as they are easily accessible and show strong osteogenic potential. In this study, we analyzed the influence of uncoated and polylactic-co-glycolic acid (PLGA)-coated β-tricalcium phosphate (β-TCP) scaffolds on JPC colonization and subsequent osteogenic differentiation. Furthermore, interaction with the human blood was investigated. This study demonstrated that PLGA-coated and uncoated β-TCP scaffolds can be colonized with JPCs and further differentiated into osteogenic cells. On day 15, after cell seeding, JPCs with and without osteogenic differentiation were incubated with fresh human whole blood under dynamic conditions. The activation of coagulation, complement system, inflammation, and blood cells were analyzed using ELISA and scanning electron microscopy (SEM). JPC-seeded scaffolds showed a dense cell layer and osteogenic differentiation capacity on both PLGA-coated and uncoated β-TCP scaffolds. SEM analyses showed no relevant blood cell attachment and ELISA results revealed no significant increase in most of the analyzed cell activation markers (β-thromboglobulin, Sc5B-9, polymorphonuclear (PMN)-elastase). However, a notable increase in thrombin-antithrombin III (TAT) complex levels, as well as fibrin fiber accumulation on JPC-seeded β-TCP scaffolds, was detected compared to the scaffolds without JPCs. Thus, this study demonstrated that besides the scaffold material the cells colonizing the scaffolds can also influence hemostasis, which can influence the regeneration of bone tissue.
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Phelipe Hatt, Luan, Keith Thompson, Werner E. G. Müller, Martin James Stoddart, and Angela Rita Armiento. "Calcium Polyphosphate Nanoparticles Act as an Effective Inorganic Phosphate Source during Osteogenic Differentiation of Human Mesenchymal Stem Cells." International Journal of Molecular Sciences 20, no. 22 (November 18, 2019): 5801. http://dx.doi.org/10.3390/ijms20225801.
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The ability of bone-marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to differentiate into osteoblasts makes them the ideal candidate for cell-based therapies targeting bone-diseases. Polyphosphate (polyP) is increasingly being studied as a potential inorganic source of phosphate for extracellular matrix mineralisation. The aim of this study is to investigate whether polyP can effectively be used as a phosphate source during the in vitro osteogenic differentiation of human BM-MSCs. Human BM-MSCs are cultivated under osteogenic conditions for 28 days with phosphate provided in the form of organic β-glycerolphosphate (BGP) or calcium-polyP nanoparticles (polyP-NP). Mineralisation is demonstrated using Alizarin red staining, cellular ATP content, and free phosphate levels are measured in both the cells and the medium. The effects of BGP or polyP-NP on alkaline phosphatase (ALP) activity and gene expression of a range of osteogenic-related markers are also assessed. PolyP-NP supplementation displays comparable effects to the classical BGP-containing osteogenic media in terms of mineralisation, ALP activity and expression of osteogenesis-associated genes. This study shows that polyP-NP act as an effective source of phosphate during mineralisation of BM-MSC. These results open new possibilities with BM-MSC-based approaches for bone repair to be achieved through doping of conventional biomaterials with polyP-NP.
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Brar, GurlalSingh, and RaviSher Singh Toor. "Dental stem cells: Dentinogenic, osteogenic, and neurogenic differentiation and its clinical cell based therapies." Indian Journal of Dental Research 23, no. 3 (2012): 393. http://dx.doi.org/10.4103/0970-9290.102239.
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Okawa, Hiroko, Hiroki Kayashima, Jun-Ichi Sasaki, Jiro Miura, Yuya Kamano, Yukihiro Kosaka, Satoshi Imazato, Hirofumi Yatani, Takuya Matsumoto, and Hiroshi Egusa. "Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells." Stem Cells International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/6240794.
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Three-dimensional (3D) cell constructs are expected to provide osteoinductive materials to develop cell-based therapies for bone regeneration. The proliferation and spontaneous aggregation capability of induced pluripotent stem cells (iPSCs) thus prompted us to fabricate a scaffold-free iPSC construct as a transplantation vehicle. Embryoid bodies of mouse gingival fibroblast-derived iPSCs (GF-iPSCs) were seeded in a cell chamber with a round-bottom well made of a thermoresponsive hydrogel. Collected ball-like cell constructs were cultured in osteogenic induction medium for 30 days with gentle shaking, resulting in significant upregulation of osteogenic marker genes. The constructs consisted of an inner region of unstructured cell mass and an outer osseous tissue region that was surrounded by osteoblast progenitor-like cells. The outer osseous tissue was robustly calcified with elemental calcium and phosphorous as well as hydroxyapatite. Subcutaneous transplantation of the GF-iPSC constructs into immunodeficient mice contributed to extensive ectopic bone formation surrounded by teratoma tissue. These results suggest that mouse GF-iPSCs could facilitate the fabrication of osteoinductive scaffold-free 3D cell constructs, in which the calcified regions and surrounding osteoblasts may function as scaffolds and drivers of osteoinduction, respectively. With incorporation of technologies to inhibit teratoma formation, this system could provide a promising strategy for bone regenerative therapies.
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Morabito, Caterina, Iolanda D'Alimonte, Laura Pierdomenico, Caterina Pipino, Simone Guarnieri, Giusy A. Caprara, Ivana Antonucci, et al. "Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells." Cellular Physiology and Biochemistry 36, no. 1 (2015): 259–73. http://dx.doi.org/10.1159/000374069.
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Background/Aims: Mesenchymal stem cells from human amniotic fluid (huAFMSCs) can differentiate into multiple lineages and are not tumorigenic after transplantation, making them good candidates for therapeutic purposes. The aim was to determine the effects of calcitonin on these huAFMSCs during osteogenic differentiation, in terms of the physiological role of calcitonin in bone homeostasis. Methods: For huAFMSCs cultured under different conditions, we assayed: expression of the calcitonin receptor, using immunolabelling techniques; proliferation and osteogenesis, using colorimetric and enzymatic assays; intracellular Ca2+ and cAMP levels, using videomicroscopy and spectrophotometry. Results: The calcitonin receptor was expressed in proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered intracellular Ca2+ increases and cAMP production. Its presence in cell medium also induced dose-dependent inhibitory effects on proliferation and increased osteogenic differentiation of huAFMSCs, as also indicated by enhancement of specific markers and alkaline phosphatase activity. Conclusions: These data show that huAFMSCs represent a potential osteogenic model to study in-vitro cell responses to calcitonin (and other members of the calcitonin family). This leads the way to the opening of new lines of research that will add new insight both in cell therapies and in the pharmacological use of these molecules.
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Wang, Yi, Xibo Ma, Wei Chai, and Jie Tian. "Multiscale Stem Cell Technologies for Osteonecrosis of the Femoral Head." Stem Cells International 2019 (January 8, 2019): 1–13. http://dx.doi.org/10.1155/2019/8914569.
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The last couple of decades have seen brilliant progress in stem cell therapies, including native, genetically modified, and engineered stem cells, for osteonecrosis of the femoral head (ONFH). In vitro studies evaluate the effect of endogenous or exogenous factor or gene regulation on osteogenic phenotype maintenance and/or differentiation towards osteogenic lineage. The preclinical and clinical outcomes accelerate the clinical translation. Bone marrow mesenchymal stem cells and adipose-derived stem cells have demonstrated better effects in the treatment of femoral head necrosis. Various materials have been used widely in the ONFH treatment in both preclinical and clinical trials. In a word, in vivo and multiscale efforts are expected to overcome obstacles in the approaches for treating ONFH and provide clinical relevance and commercial strategies in the future. Therefore, we will discuss the above aspects in this paper and present our opinions.
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Labedz-Maslowska, Anna, Natalia Bryniarska, Andrzej Kubiak, Tomasz Kaczmarzyk, Malgorzata Sekula-Stryjewska, Sylwia Noga, Dariusz Boruczkowski, Zbigniew Madeja, and Ewa Zuba-Surma. "Multilineage Differentiation Potential of Human Dental Pulp Stem Cells—Impact of 3D and Hypoxic Environment on Osteogenesis In Vitro." International Journal of Molecular Sciences 21, no. 17 (August 26, 2020): 6172. http://dx.doi.org/10.3390/ijms21176172.
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Human dental pulp harbours unique stem cell population exhibiting mesenchymal stem/stromal cell (MSC) characteristics. This study aimed to analyse the differentiation potential and other essential functional and morphological features of dental pulp stem cells (DPSCs) in comparison with Wharton’s jelly-derived MSCs from the umbilical cord (UC-MSCs), and to evaluate the osteogenic differentiation of DPSCs in 3D culture with a hypoxic microenvironment resembling the stem cell niche. Human DPSCs as well as UC-MSCs were isolated from primary human tissues and were subjected to a series of experiments. We established a multiantigenic profile of DPSCs with CD45−/CD14−/CD34−/CD29+/CD44+/CD73+/CD90+/CD105+/Stro-1+/HLA-DR− (using flow cytometry) and confirmed their tri-lineage osteogenic, chondrogenic, and adipogenic differentiation potential (using qRT-PCR and histochemical staining) in comparison with the UC-MSCs. The results also demonstrated the potency of DPSCs to differentiate into osteoblasts in vitro. Moreover, we showed that the DPSCs exhibit limited cardiomyogenic and endothelial differentiation potential. Decreased proliferation and metabolic activity as well as increased osteogenic differentiation of DPSCs in vitro, attributed to 3D cell encapsulation and low oxygen concentration, were also observed. DPSCs exhibiting elevated osteogenic potential may serve as potential candidates for a cell-based product for advanced therapy, particularly for bone repair. Novel tissue engineering approaches combining DPSCs, 3D biomaterial scaffolds, and other stimulating chemical factors may represent innovative strategies for pro-regenerative therapies.
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Osagie-Clouard, Liza, Anita Sanghani-Kerai, Melanie Coathup, Richard Meeson, Timothy Briggs, and Gordon Blunn. "The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats." Bone & Joint Research 8, no. 8 (August 2019): 397–404. http://dx.doi.org/10.1302/2046-3758.88.bjr-2019-0018.r1.
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Objectives Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Methods Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. Results Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. Conclusion Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies. Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397–404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1.
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Cao, Yangyang, Haoqing Yang, Luyuan Jin, Juan Du, and Zhipeng Fan. "Genome-Wide DNA Methylation Analysis during Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells." Stem Cells International 2018 (September 10, 2018): 1–11. http://dx.doi.org/10.1155/2018/8238496.
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Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising candidates in cell-based therapy for the regeneration of damaged bone tissues that are either incurable or intractable due to the insufficiency of current therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and that this differentiation is regulated by some specific patterns of epigenetic modifications, such as DNA methylation. However, the potential role of DNA methylation modification in BMSC osteogenic differentiation is unclear. In this study, we performed a genome-wide study of DNA methylation between the noninduced and induced osteogenic differentiation of BMSCs at day 7. We found that the majority of cytosines in a CpG context were methylated in induced BMSCs. Our results also revealed that, along with the induced osteogenic differentiation in BMSCs, the average genomic methylation levels and CpG methylation in transcriptional factor regions (TFs) were increased, the CpG methylation level of various genomic elements was mainly in the medium-high methylation section, and CpG methylation levels in the repeat element had highly methylated levels. The GO analysis of differentially methylated region- (DMR-) associated genes (DMGs) showed that GO terms, including cytoskeletal protein binding (included in Molecular Function GO terms), skeletal development (included in Biological Process GO terms), mesenchymal cell differentiation (included in Biological Process GO terms), and stem cell differentiation (included in Biological Process), were enriched in the hypermethylated DMGs. Then, the KEGG analysis results showed that the WNT pathway, inositol phosphate metabolism pathway, and cocaine addiction pathway were more correlative with the DMRs during the induced osteogenic differentiation in BMSCs. In conclusion, this study revealed the difference of methylated levels during the noninduced and induced osteogenic differentiation of BMSCs and provided useful information for future works to characterize the important function of epigenetic mechanisms on BMSCs’ differentiation.
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Ena, Sabrina, Julia Ino, Aurelie Neirinck, Sandra Pietri, Anna Tury, and Enrico Bastianelli. "Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue." Journal of Medicines Development Sciences 1, no. 2 (December 31, 2017): 12. http://dx.doi.org/10.18063/jmds.v1i2.135.
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Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo.
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Ena, Sabrina, Julia Ino, Aurelie Neirinck, Sandra Pietri, Anna Tury, and Enrico Bastianelli. "Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue." Journal of Medicines Development Sciences 1, no. 2 (December 31, 2015): 12. http://dx.doi.org/10.18063/jmds.2015.02.004.
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Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo.
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Chen, Jishizhan, Jia Hua, and Wenhui Song. "Screen Key Genes Associated with Distraction-Induced Osteogenesis of Stem Cells Using Bioinformatics Methods." International Journal of Molecular Sciences 22, no. 12 (June 17, 2021): 6505. http://dx.doi.org/10.3390/ijms22126505.
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Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies.
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Gambari, Laura, Marli Barone, Emanuela Amore, Brunella Grigolo, Giuseppe Filardo, Renato Iori, Valentina Citi, Vincenzo Calderone, and Francesco Grassi. "Glucoraphanin Increases Intracellular Hydrogen Sulfide (H2S) Levels and Stimulates Osteogenic Differentiation in Human Mesenchymal Stromal Cell." Nutrients 14, no. 3 (January 19, 2022): 435. http://dx.doi.org/10.3390/nu14030435.
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Osteopenia and osteoporosis are among the most prevalent consequences of ageing, urging the promotion of healthy nutritional habits as a tool in preventing bone fractures. Glucosinolates (GLSs) are organosulfur compounds considered relatively inert precursors of reactive derivatives isothiocyanates (ITCs). Recent evidence suggests that GLSs may exert biological properties based on their capacity to release hydrogen sulfide (H2S). H2S-donors are known to exert anabolic function on bone cells. Here, we investigated whether a GLS, glucoraphanin (GRA) obtained from Tuscan black kale, promotes osteogenesis in human mesenchymal stromal cells (hMSCs). H2S release in buffer and intracellular H2S levels were detected by amperometric measurements and fluorimetric/cytofluorimetric analyses, respectively. Alizarin red staining assay and real-time PCR were performed to evaluate mineral apposition and mRNA expression of osteogenic genes. Using an in vitro cell culture model, our data demonstrate a sulforaphane (SFN)-independent osteogenic stimulation of GRA in hMSCs, at least partially attributable to H2S release. In particular, GRA upregulated the expression of osteogenic genes and enhanced mineral apposition while increasing intracellular concentrations of H2S. Overall, this study suggests the feasibility of using cruciferous derivatives as natural alternatives to chemical H2S-donors as adjuvant therapies in the treatment of bone-wasting diseases.
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Takabatake, Kiyofumi, Masakazu Matsubara, Eiki Yamachika, Yuki Fujita, Yuki Arimura, Kazuki Nakatsuji, Keisuke Nakano, Histoshi Nagatsuka, and Seiji Iida. "Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method." International Journal of Molecular Sciences 22, no. 22 (November 17, 2021): 12392. http://dx.doi.org/10.3390/ijms222212392.
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Background: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). Method: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. Results: The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. Conclusion: DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies.
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Xu, Yan, Tao Zhang, Yang Chen, Qiang Shi, Muzhi Li, Tian Qin, Jianzhong Hu, Hongbin Lu, Jun Liu, and Can Chen. "Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells." Stem Cells International 2020 (September 29, 2020): 1–12. http://dx.doi.org/10.1155/2020/8894449.
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Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.
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Barba, Marta, Claudia Cicione, Camilla Bernardini, Vincenzo Campana, Ernesto Pagano, Fabrizio Michetti, Giandomenico Logroscino, and Wanda Lattanzi. "Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches." Scientific World Journal 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/406159.
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Bone fusion represents a challenge in the orthopedics practice, being especially indicated for spine disorders. Spinal fusion can be defined as the bony union between two vertebral bodies obtained through the surgical introduction of an osteoconductive, osteoinductive, and osteogenic compound. Autogenous bone graft provides all these three qualities and is considered the gold standard. However, a high morbidity is associated with the harvest procedure. Intensive research efforts have been spent during the last decades to develop new approaches and technologies for successful spine fusion. In recent years, cell and gene therapies have attracted great interest from the scientific community. The improved knowledge of both mesenchymal stem cell biology and osteogenic molecules allowed their use in regenerative medicine, representing attractive approaches to achieve bone regeneration also in spinal surgery applications. In this review we aim to describe the developing gene- and cell-based bone regenerative approaches as promising future trends in spine fusion.
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Heo, June Seok, Seung Gwan Lee, and Hyun Ok Kim. "The Flavonoid Glabridin Induces OCT4 to Enhance Osteogenetic Potential in Mesenchymal Stem Cells." Stem Cells International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/6921703.
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Mesenchymal stem cells (MSCs) are a promising tool for studying intractable diseases. Unfortunately, MSCs can easily undergo cellular senescence during in vitro expansion by losing stemness. The aim of this study was to improve the stemness and differentiation of MSCs by using glabridin, a natural flavonoid. Assessments of cell viability, cell proliferation, β-galactosidase activity, differentiation, and gene expression by reverse transcription PCR were subsequently performed in the absence or presence of glabridin. Glabridin enhanced the self-renewal capacity of MSCs, as indicated by the upregulation of the OCT4 gene. In addition, it resulted in an increase in the osteogenic differentiation potential by inducing the expression of osteogenesis-related genes such as DLX5 and RUNX2. We confirmed that glabridin improved the osteogenesis of MSCs with a significant elevation in the expression of OSTEOCALCIN and OSTEOPONTIN genes. Taken together, these results suggest that glabridin enhances osteogenic differentiation of MSCs with induction of the OCT4 gene; thus, glabridin could be useful for stem cell-based therapies.
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Chung, Rosa, and Cory J. Xian. "RECENT RESEARCH ON THE GROWTH PLATE: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration." Journal of Molecular Endocrinology 53, no. 1 (August 2014): T45—T61. http://dx.doi.org/10.1530/jme-14-0062.
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Injuries to the growth plate cartilage often lead to bony repair, resulting in bone growth defects such as limb length discrepancy and angulation deformity in children. Currently utilised corrective surgeries are highly invasive and limited in their effectiveness, and there are no known biological therapies to induce cartilage regeneration and prevent the undesirable bony repair. In the last 2 decades, studies have investigated the cellular and molecular events that lead to bony repair at the injured growth plate including the identification of the four phases of injury repair responses (inflammatory, fibrogenic, osteogenic and remodelling), the important role of inflammatory cytokine tumour necrosis factor alpha in regulating downstream repair responses, the role of chemotactic and mitogenic platelet-derived growth factor in the fibrogenic response, the involvement and roles of bone morphogenic protein and Wnt/B-catenin signalling pathways, as well as vascular endothelial growth factor-based angiogenesis during the osteogenic response. These new findings could potentially lead to identification of new targets for developing a future biological therapy. In addition, recent advances in cartilage tissue engineering highlight the promising potential for utilising multipotent mesenchymal stem cells (MSCs) for inducing regeneration of injured growth plate cartilage. This review aims to summarise current understanding of the mechanisms for growth plate injury repair and discuss some progress, potential and challenges of MSC-based therapies to induce growth plate cartilage regeneration in combination with chemotactic and chondrogenic growth factors and supporting scaffolds.
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Gutiérrez, David, Mahmoud Rouabhia, Javiera Ortiz, Diego Gaviria, Camilo Alfonso, Ana Muñoz, and Carolina Inostroza. "Low-Level Laser Irradiation Promotes Proliferation and Differentiation on Apical Papilla Stem Cells." Journal of Lasers in Medical Sciences 12, no. 1 (December 1, 2021): e75-e75. http://dx.doi.org/10.34172/jlms.2021.75.
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Introduction: Low-level laser therapy (LLLT) has been reported to improve cell proliferation and differentiation. The stem cells derived from dental apical papilla (SCAPs) are a promising therapy because they are easily obtained from immature human teeth. The effect of LLLT over SCAPs is still unknown. This study aimed to evaluate the proliferation and osteogenic potential of the SCAPs stimulated with LLLT. Methods: SCAPs were isolated from the third molars of a healthy donor and characterized according to the minimum established criteria. SCAPs were cultured for 24 hours before being exposed to LLLT. Cells were exposed to different doses, energy, and wavelengths for selecting the irradiation parameters. SCAPs proliferation was evaluated with the MTT assay at 24 hours and 7-day post-laser exposure. VEGF and TGFβ2 expression were assessed with a specific enzyme-linked immunosorbent assay (ELISA). The osteogenic differentiation potential was analyzed with alizarin red staining, and the nodule quantification was performed by the relative optical density (ROD) analysis using ImageJ software. Results: The cells isolated from the apical papilla showed phenotype and stem cell properties. SCAPs irradiated with one dose at 6 J/m2 and 650 nm exhibited significantly higher proliferation (P>0.05) than the controls nonirradiated. LLLT stimulated SCAPs’ expression of factors VEGF and TGFβ2. Also, SCAPs irradiated showed higher osteogenic activity (P<0.05). Conclusion: LLLT promotes proliferation, osteogenic differentiation, and VEGF and TGFβ2 expression on SCAPs. LLLT is a practical approach for the preconditioning of SCAPs in vitro for future regenerative therapies. More studies are needed to determine the underlying molecular processes that determine the mechanism of the LLLT.
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Yuan, Ye, Gege Yan, Rui Gong, Lai Zhang, Tianyi Liu, Chao Feng, Weijie Du, et al. "Effects of Blue Light Emitting Diode Irradiation On the Proliferation, Apoptosis and Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells." Cellular Physiology and Biochemistry 43, no. 1 (2017): 237–46. http://dx.doi.org/10.1159/000480344.
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Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrow-derived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS production and DNA damage. Conclusions: Taken together, our study demonstrated that blue LED light inhibited cell proliferation, inhibited osteogenic differentiation, and induced apoptosis in BMSCs, which are associated with increased ROS production and DNA damage. These findings may provide important insights for the application of LEDs in future BMSC-based therapies.
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Wang, Li, Fulu Jin, Peiyu Wang, Shiqiang Hou, Tao Jin, Xiansong Chang, and Liangping Zhao. "Adropin Inhibits Vascular Smooth Muscle Cell Osteogenic Differentiation to Alleviate Vascular Calcification via the JAK2/STAT3 Signaling Pathway." BioMed Research International 2022 (July 27, 2022): 1–10. http://dx.doi.org/10.1155/2022/9122264.
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Vascular calcification is characterized as the deposition of hydroxyapatite mineral in the form of calcium-phosphate complexes in the vasculature. Transdifferentiation between vascular smooth muscle cells (VSMCs) and osteoblast-like cells is considered essential in the progression of vascular calcification. The pathophysiological mechanisms underlying vascular calcification and VSMC osteogenic differentiation remain to be fully elucidated, and the development of novel therapies is required. In the present study, PCR and western blot analysis were conducted to quantify the mRNA and protein expression levels of calcification-associated markers (bone morphogenetic protein 2, alkaline phosphatase, osteoprotegerin, osteocalcin, and runt-related transcription factor 2) and adropin in VSMCs and rat vascular tissues. The calcification of VSMCs was assessed using alizarin red staining. Moreover, adropin expression levels in VSMCs were analyzed using immunofluorescence. Lentiviral transfection and small interfering RNA were used for overexpression and knockdown of adropin in VSMCs, respectively. The results demonstrated that adropin alleviated vascular calcification in vivo. Moreover, adropin also inhibited osteogenic differentiation and the calcification of VSMCs in vitro. Notably, results of the present study revealed that the tyrosine protein kinase JAK2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway played a key role in the aforementioned inhibition. In conclusion, the results of the present study demonstrated that adropin inhibited VSMC osteogenic differentiation to alleviate vascular calcification via the JAK2/STAT3 signaling pathway.
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Nováková, Slavomíra, Maksym Danchenko, Terézia Okajčeková, Eva Baranovičová, Andrej Kováč, Marián Grendár, Gábor Beke, et al. "Comparative Proteomic and Metabolomic Analysis of Human Osteoblasts, Differentiated from Dental Pulp Stem Cells, Hinted Crucial Signaling Pathways Promoting Osteogenesis." International Journal of Molecular Sciences 22, no. 15 (July 24, 2021): 7908. http://dx.doi.org/10.3390/ijms22157908.
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Population aging has been a global trend for the last decades, which increases the pressure to develop new cell-based or drug-based therapies, including those that may cure bone diseases. To understand molecular processes that underlie bone development and turnover, we followed osteogenic differentiation of human dental pulp stem cells (DPSCs) using a specific induction medium. The differentiation process imitating in vivo osteogenesis is triggered by various signaling pathways and is associated with massive proteome and metabolome changes. Proteome was profiled by ultrahigh-performance liquid chromatography and comprehensively quantified by ion mobility-enhanced mass spectrometry. From 2667 reproducibly quantified and identified proteins, 432 were differentially abundant by strict statistic criteria. Metabolome profiling was carried out by nuclear magnetic resonance. From 27 detected metabolites, 8 were differentially accumulated. KEGG and MetaboAnalyst hinted metabolic pathways that may be involved in the osteogenic process. Enrichment analysis of differentially abundant proteins highlighted PPAR, FoxO, JAK-STAT, IL-17 signaling pathways, biosynthesis of thyroid hormones and steroids, mineral absorption, and fatty acid metabolism as processes with prominent impact on osteoinduction. In parallel, metabolomic data showed that aminoacyl-tRNA biosynthesis, as well as specific amino acids, likely promote osteodifferentiation. Targeted immunoassays validated and complemented omic results. Our data underlined the complexity of the osteogenic mechanism. Finally, we proposed promising targets for future validation in patient samples, a step toward the treatment of bone defects.
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Rožanc, Jan, Lidija Gradišnik, Tomaž Velnar, Minja Gregorič, Marko Milojević, Boštjan Vihar, Boris Gole, and Uroš Maver. "Mesenchymal Stem Cells Isolated from Paediatric Paravertebral Adipose Tissue Show Strong Osteogenic Potential." Biomedicines 10, no. 2 (February 4, 2022): 378. http://dx.doi.org/10.3390/biomedicines10020378.
Full textAbstract:
Mesenchymal stem cells (MSCs) represent the basis of novel clinical concepts in cellular therapy and tissue regeneration. Therefore, the isolation of MSCs from various tissues has become an important endeavour for stem cell biobanking and the development of regenerative therapies. Paravertebral adipose tissue is readily exposed during spinal procedures in children and could be a viable source of stem cells for therapeutic applications. Here, we describe the first case of MSCs isolated from paravertebral adipose tissue (PV-ADMSCs), obtained during a routine spinal surgery on a child. Using quantitative real-time PCR and flow cytometry, we show that PV-ADMSCs have different levels of stem marker expression compared to the MSCs from other sources while having the highest proliferation rate. Furthermore, we evaluate the multipotency of PV-ADMSCs by the three-lineage (adipogenic, osteogenic and chondrogenic) differentiation and compare it to the multipotency of MSCs from other sources. It was found that the PV-ADMSCs have a strong osteogenic potential in particular. Taken together, our data indicate that PV-ADMSCs meet the criteria for successful cell therapy, defined by the International Society for Cellular Therapy (ISCT), and thus, could provide a source of MSCs that is relatively easy to isolate and expand in culture. Due to their strong osteogenic potential, these cells provide a promising basis, especially for orthopaedic applications.
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Asensio, Gerardo, Marcela Martín-del-Campo, Rosa Ana Ramírez, Luis Rojo, and Blanca Vázquez-Lasa. "New Insights into the In Vitro Antioxidant Routes and Osteogenic Properties of Sr/Zn Phytate Compounds." Pharmaceutics 15, no. 2 (January 19, 2023): 339. http://dx.doi.org/10.3390/pharmaceutics15020339.
Full textAbstract:
Sr/Zn phytate compounds have been shown interest in biomaterial science, specifically in dental implantology, due to their antimicrobial effects against Streptococcus mutans and their capacity to form bioactive coatings. Phytic acid is a natural chelating compound that shows antioxidant and osteogenic properties that can play an important role in bone remodelling processes affected by oxidative stress environments, such as those produced during infections. The application of non-protein cell-signalling molecules that regulate both bone and ROS homeostasis is a promising strategy for the regeneration of bone tissues affected by oxidative stress processes. In this context, phytic acid (PA) emerged as an excellent option since its antioxidant and osteogenic properties can play an important role in bone remodelling processes. In this study, we explored the antioxidant and osteogenic properties of two metallic PA complexes bearing bioactive cations, i.e., Sr2+ (SrPhy) and Zn2+ (ZnPhy), highlighting the effect of the divalent cations anchored to phytate moieties and their capability to modulate the PA properties. The in vitro features of the complexes were analyzed and compared with those of their precursor PA. The ferrozine/FeCl2 method indicated that SrPhy exhibited a more remarkable ferrous ion affinity than ZnPhy, while the antioxidant activity demonstrated by a DPPH assay showed that only ZnPhy reduced the content of free radicals. Likewise, the antioxidant potential was assessed with RAW264.7 cell cultures. An ROS assay indicated again that ZnPhy was the only one to reduce the ROS content (20%), whereas all phytate compounds inhibited lipid peroxidation following the decreasing order of PA > SrPhy > ZnPhy. The in vitro evaluation of the phytate’s osteogenic ability was performed using hMSC cells. The results showed tailored properties related to the cation bound in each complex. ZnPhy overexpressed ALP activity at 3 and 14 days, and SrPhy significantly increased calcium deposition after 21 days. This study demonstrated that Sr/Zn phytates maintained the antioxidant and osteogenic properties of PA and can be used in bone regenerative therapies involving oxidative environments, such as infected implant coatings and periodontal tissues.
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Abarrategi, Ander, Juan Tornin, Lucia Martinez-Cruzado, Ashley Hamilton, Enrique Martinez-Campos, Juan P. Rodrigo, M. Victoria González, Nicola Baldini, Javier Garcia-Castro, and Rene Rodriguez. "Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies." Stem Cells International 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/3631764.
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Osteosarcoma (OS) is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.
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Petrella, Francesco, Stefania Rizzo, Alessandro Borri, Monica Casiraghi, and Lorenzo Spaggiari. "Current Perspectives in Mesenchymal Stromal Cell Therapies for Airway Tissue Defects." Stem Cells International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/746392.
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Lung cancer is the leading cause of cancer death and respiratory diseases are the third cause of death in industrialized countries; for this reason the airways and cardiopulmonary system have been the focus of extensive investigation, in particular of the new emerging branch of regenerative medicine. Mesenchymal stromal cells (MSCs) are a population of undifferentiated multipotent adult cells that naturally reside within the human body, which can differentiate into osteogenic, chondrogenic, and adipogenic lineages when cultured in specific inducing media. MSCs have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation and differentiation into specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. Experimental and clinical evidence exists regarding MSCs efficacy in airway defects restoration; although clinical MSCs use, in the daily practice, is not yet completely reached for airway diseases, we can argue that MSCs do not represent any more merely an experimental approach to airway tissue defects restoration but they can be considered as a “salvage” therapeutic tool in very selected patients and diseases.
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Lee, Ching-Yu, Tsung-Jen Huang, Meng-Huang Wu, Yen-Yao Li, and Kuan-Der Lee. "High Expression of Acid-Sensing Ion Channel 2 (ASIC2) in Bone Cells in Osteoporotic Vertebral Fractures." BioMed Research International 2019 (August 19, 2019): 1–10. http://dx.doi.org/10.1155/2019/4714279.
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Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). This study delineated ASICs expression in adult human bone marrow-mesenchymal stem cells- (BM-MSC-) derived osteoblasts and in OVF bone cells. Adult BM-MSC-derived osteoblasts were isolated and cultured in different pH values. Osteogenic markers as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OC) mRNA were assessed. Western blots method was applied to analyze ASICs protein expression in different pH values. Amiloride was added into the osteogenic media to analyze the Na+/K+ ATPase change. We harvested the vertebral cancellous bone through a bone biopsy needle in 26 OVF patients when performing percutaneous vertebroplasty. Six vertebral bone specimens obtained from 4 patients with high-energy vertebral fractures were used as the control. The reverse transcription polymerase chain reaction was performed to analyze the quantitative mRNA expression of ASICs. Osteogenic markers as ALP, OPN, and OC mRNA were higher expressed in increasing pH values throughout osteoblastogenesis. ASIC proteins were higher expressed in lower pH media, especially ASIC3, and ASIC4. The highest protein expression at days 7, 14, and 21 was ASIC2, ASIC4, and ASIC3, respectively. Expression of Na+/K+ ATPase was significantly decreased in cultured osteoblasts by addition of amiloride into the pH 6.9 osteogenic media. ASIC2 mRNA was most highly expressed with a 65.93-fold increase in the biopsied vertebral bone cells in OVF compared with the control. In conclusion, we found osteoblastogenesis was reduced in an acidic environment, and ASIC2, ASIC3, and ASIC4 were most highly expressed in turn during osteoblastogenesis within acidic media. ASIC2 was the most abundantly expressed gene in human bone cells in OVF compared with the control. ASIC2 could be crucial in the pathogenesis of osteoporosis and could serve as a therapeutic target for antiosteoporotic therapies.
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Siegel, L., T. Bane, J. Bertels, K. Ratz, M. Rubessa, and M. Wheeler. "184 Effect of selenium on the differentiation of porcine adipose-derived stem cells into osteoblasts." Reproduction, Fertility and Development 31, no. 1 (2019): 216. http://dx.doi.org/10.1071/rdv31n1ab184.
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Bone damage is a common occurrence and although traditional bone healing methods work well, they are not always able to fix all issues pertaining to the injury. However, recent research on stem cell therapies using adipose-derived stem cells (ASC) has shown that ASC that differentiate into osteoblasts can be used as a potentially better solution for bone injuries. Selenium is a nutritional trace element that has been found to be essential in the production of selenoproteins and bone growth. Selenium plays an integral role in osteoblast cell differentiation and proliferation. The aim of this experiment was to test whether adding selenium to osteogenic influences the differentiation potential of ASC into osteoblasts. Porcine ASC were isolated as described (Monaco et al. 2009, Open Tissue Eng. Regen. Med. J. 2, 20-33). Seven different treatments were given to the cells: a negative control of DMEM, a positive control of osteogenic medium, and 5 concentrations of selenium in the osteogenic medium (10, 5, 1, 0.5, and 0.1 µM). Medium was changed twice a week for 4 weeks, at the end of which the cells were stained with Alizarin Red S stain. The number of osteoblastic nodules in each well were counted and divided into the categories of “forming” and “formed.” A generalized linear model (GLM) procedure (SPSS Inc./IBM Corp., Chicago, IL, USA) was used to analyse the data. The least statistical difference (l.s.d.) post hoc test was used to perform statistical multiple comparison with an α-level of 0.05. The results showed (Table 1) that medium containing selenium concentrations of 0.1, 0.5, and 1.0 µM were able to develop more nodules than the osteogenic medium. There was no statistical difference in the total amount of forming and formed nodules in those 4 groups; however, there was a statistical tendency for a difference (P=0.06) between the medium with 1 µM selenium and the osteogenic medium. Medium containing 10 or 5 µM selenium had lower nodule counts (both forming and formed) than osteogenic medium. There was no statistical difference between 10 µM and DMEM. These results suggest that low concentrations of selenium have a positive effect on nodule formation, whereas higher concentrations are detrimental. Table 1.The average number (standard deviations in parentheses) of formed, forming, and total osteoblastic nodules in each of the different treatments
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Meyers, P. A., G. Heller, J. H. Healey, A. Huvos, A. Applewhite, M. Sun, and M. LaQuaglia. "Osteogenic sarcoma with clinically detectable metastasis at initial presentation." Journal of Clinical Oncology 11, no. 3 (March 1993): 449–53. http://dx.doi.org/10.1200/jco.1993.11.3.449.
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PURPOSE Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease. PATIENTS AND METHODS From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease. RESULTS Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival. CONCLUSION OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.
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Stefańska, Katarzyna, Katarzyna Ożegowska, Greg Hutchings, Małgorzata Popis, Lisa Moncrieff, Claudia Dompe, Krzysztof Janowicz, et al. "Human Wharton’s Jelly—Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials." Journal of Clinical Medicine 9, no. 4 (April 12, 2020): 1102. http://dx.doi.org/10.3390/jcm9041102.
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Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton’s jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton’s jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton’s jelly, is a promising source of mesenchymal stem cells.