Academic literature on the topic 'Bone marrow adipocytes'
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Journal articles on the topic "Bone marrow adipocytes"
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Naveiras, Olaia, Valentina Nardi, and George Q. Daley. "Bone Marrow Adipocytes Prevent Hematopoietic Expansion in Homeostasis and in Bone Marrow Transplantation." Blood 112, no. 11 (November 16, 2008): 551. http://dx.doi.org/10.1182/blood.v112.11.551.551.
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Abstract In mammalian bone marrow (BM), osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC). Adult BM also contains numerous adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. As described by Neumann’s law in 1882, distal skeletal regions are adipocytic and thus non-hematopoietic in the adult. Fatty infiltration of the hematopoietic red marrow also occurs following irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. However, whether adipocytes participate in hematopoietic regulation or simply expand to fill marrow space is unclear. We have found that murine hematopoiesis is reduced in adipocyte-rich marrow during homeostasis, and that adipocytes antagonize marrow recovery post-irradiation. By flow cytometry, colony forming assay, and competitive repopulation, we found a reduced frequency of HSCs and short-term hematopoietic progenitors in the adipocyte-rich vertebrae of the tail compared to the adipocyte-free vertebrae of the thorax. In A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes, post-irradiation marrow engraftment is accelerated relative to wild type mice. Likewise, pharmacologic inhibition of adipocyte formation with the PPARg inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE) enhances hematopoietic recovery after BM transplant. Moreover, we have found that mice deficient in the adipocyte-specific protein adiponectin, which has been described to inhibit hematopoietic progenitor expansion in vitro, have increased progenitors in fatty marrow both during homeostasis and after BM transplant. Our data implicate adipocytes as negative regulators of the bone marrow microenvironment, and demonstrate that antagonizing adipogenesis is advantageous for enhancing hematopoietic recovery in the setting of bone marrow transplantation.
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Yang, S., W. Lu, C. Zhao, Y. Zhai, Y. Wei, J. Liu, Y. Yu, Z. Li, and J. Shi. "PF457 MECHANISM OF MORPHOLOGICAL REMODELING OF BONE MARROW ADIPOCYTES IN ACUTE MYELOID LEUKEMIA." HemaSphere 3, S1 (June 2019): 180. http://dx.doi.org/10.1002/j.2572-9241.2019.tb00056.x.
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Background:We have previously found that morphological remodeling of bone marrow adipocytes in acute myeloid leukemia (AML) patients is closely related to poor prognosis, and growth differentiation factor 15 (GDF15) may be a key factor in this pathological phenomenon.Aims:In this study, we further explored the mechanism of GDF15 regulating the bone marrow adipocyte remodeling from the perspective of calcium channel TRPV4.Methods:GDF15‐induced adipocytes were analyzed using gene expression profiling, and gene knockdown cells were generated by lentiviral‐mediated shRNA. Chip‐qPCR was used to evaluate the interaction between transcription factors and TRPV4. Signaling pathway downstream of GDF15 involved in adipocytes was analyzed by inhibitor experiments. An experimental AML mouse model was generated to investigate the role of TRPV4 in leukemia cell‐induced bone marrow adipocyte remodeling.Results:Western blot and RT‐qPCR showed that GDF15 could regulate TRPV4 expression in bone marrow adipocytes. In vitro, Transwell assay and neutralizing antibody assay further found that GDF15 secreted by leukemia cells regulated bone marrow adipocyte remodeling through TRPV4. The phenomenon was verified in obese C57/BL6 mice. Specific inhibition experiments showed that GDF15 secreted by leukemia cells combined with TGFβRII in bone marrow adipocytes, and then activated PI3K / AKT pathway. Using RNA‐Seq technique, we found that transcription factor FOXC1 mediated the inhibition of GDF15 on TRPV4 expression in bone marrow adipocytes, which causes the morphological remodeling of bone marrow adipocytes.Summary/Conclusion:GDF15 secreted by leukemia cells inhibits the expression of TRPV4 by regulating the transcription factor FOXC1 in bone marrow adipocytes, which promote the lipolysis of adipocytes. The free fatty acids released by this process provide energy support for the growth of leukemia cells. This paper provides a new perspective for the study of leukemia cell remodeling of bone marrow adipocyte microenvironment.
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Kwak, Jun-Goo, and Jungwoo Lee. "Bone Marrow Adipocytes Contribute to Tumor Microenvironment-Driven Chemoresistance via Sequestration of Doxorubicin." Cancers 15, no. 10 (May 12, 2023): 2737. http://dx.doi.org/10.3390/cancers15102737.
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Chemoresistance is a significant problem in the effective treatment of bone metastasis. Adipocytes are a major stromal cell type in the bone marrow and may play a crucial role in developing microenvironment-driven chemoresistance. However, detailed investigation remains challenging due to the anatomical inaccessibility and intrinsic tissue complexity of the bone marrow microenvironment. In this study, we developed 2D and 3D in vitro models of bone marrow adipocytes to examine the mechanisms underlying adipocyte-induced chemoresistance. We first established a protocol for the rapid and robust differentiation of human bone marrow stromal cells (hBMSCs) into mature adipocytes in 2D tissue culture plastic using rosiglitazone (10 μM), a PPARγ agonist. Next, we created a 3D adipocyte culture model by inducing aggregation of hBMSCs and adipogenesis to create adipocyte spheroids in porous hydrogel scaffolds that mimic bone marrow sinusoids. Simulated chemotherapy treatment with doxorubicin (2.5 μM) demonstrated that mature adipocytes sequester doxorubicin in lipid droplets, resulting in reduced cytotoxicity. Lastly, we performed direct coculture of human multiple myeloma cells (MM1.S) with the established 3D adipocyte model in the presence of doxorubicin. This resulted in significantly accelerated multiple myeloma proliferation following doxorubicin treatment. Our findings suggest that the sequestration of hydrophobic chemotherapeutics by mature adipocytes represents a potent mechanism of bone marrow microenvironment-driven chemoresistance.
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Lecka-Czernik, Beata, and Larry J. Suva. "Resolving the Two “Bony” Faces of PPAR-γ." PPAR Research 2006 (2006): 1–9. http://dx.doi.org/10.1155/ppar/2006/27489.
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Bone loss with aging results from attenuated and unbalanced bone turnover that has been associated with a decreased number of bone forming osteoblasts, an increased number of bone resorbing osteoclasts, and an increased number of adipocytes (fat cells) in the bone marrow. Osteoblasts and adipocytes are derived from marrow mesenchymal stroma/stem cells (MSC). The milieu of intracellular and extracellular signals that controls MSC lineage allocation is diverse. The adipocyte-specific transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) acts as a critical positive regulator of marrow adipocyte formation and as a negative regulator of osteoblast development.In vivo, increased PPAR-γactivity leads to bone loss, similar to the bone loss observed with aging, whereas decreased PPAR-γactivity results in increased bone mass. Emerging evidence suggests that the pro-adipocytic and the anti-osteoblastic properties of PPAR-γare ligand-selective, suggesting the existence of multiple mechanisms by which PPAR-γcontrols bone mass and fat mass in bone.
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Liu, Huan, Jin He, Su Pin Koh, Yuping Zhong, Zhiqiang Liu, Zhiqiang Wang, Yujin Zhang, et al. "Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease." Science Translational Medicine 11, no. 494 (May 29, 2019): eaau9087. http://dx.doi.org/10.1126/scitranslmed.aau9087.
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Osteolytic lesions in multiple myeloma are caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing after successful treatment. We observed adipocytes on trabecular bone near the resorbed area in successfully treated patients. Normal marrow adipocytes, when cocultured with myeloma cells, were reprogrammed and produced adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator–activated receptor γ (PPARγ) mediated by recruitment of polycomb repressive complex 2 (PRC2), which modifies PPARγ promoter methylation at trimethyl lysine-27 histone H3. We confirmed the importance of methylation in the PPARγ promoter by demonstrating that adipocyte-specific knockout of EZH2, a member of the PRC2, prevents adipocyte reprogramming and reverses bone changes in a mouse model. We validated the strong correlation between the frequency of bone lesions and the expression of EZH2 in marrow adipocytes from patients in remission. These results define a role for adipocytes in genesis of myeloma-associated bone disease and that reversal of adipocyte reprogramming has therapeutic implications.
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Jin, Linhua, Marina Konopleva, Yixin Zhou, Akimichi Osaka, Michael Andreeff, Takashi Miida, and Yoko Tabe. "Pro-Apoptotic and Proliferative Effects of Bone Marrow Adipocytes on Myeloid Leukemia Cells." Blood 114, no. 22 (November 20, 2009): 4572. http://dx.doi.org/10.1182/blood.v114.22.4572.4572.
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Abstract Abstract 4572 Bone marrow stromal cells (MSCs) from elderly subjects have a reduced capacity to differentiate into osteoblasts and an increased capacity to differentiate into adipocytes, which leads to progressive accumulation of fat in the bone marrow space with increasing age. Adipocytes are the prevalent stromal cell type in adult BM that play an important role in the leukemic bone marrow microenvironment (Tabe et al., Blood 2004 103:1815-22). In this study, we examined the role of BM-derived adipocytes at different stages of differentiation on proliferation and apoptosis of AML cells. U937 cells were co-cultured with BM-derived MSC, MSC-differentiated pre-adipocytes (containing few small lipid vesicles), and mature adipocytes (with multiple hypertrophic lipid vesicules). Under serum-starved conditions, MSC and premature/mature adipocytes induced cell cycle progression of U937 cells with increase in the proportion of cells in S- and G2/M-phase fractions, and inhibited spontaneous cell death with decrease in subG1 fractions. However, only pre-adipocytes inhibited Ara-C-induced cell killing (Table 1). We next focused on lepin and plasminogen activator inhibitor 1(PAI-1) as potential mediators of these effects by adipocytes. Leptin mRNA and protein levels were upregulated during adipocytic differentiation (mRNA relative expression to GAPDH (PCR): MSC 0, premature adipocyte 2.0±0.5, mature adipocyte 123.3± 35.0; leptin secretion: MSC 23.1±2.9, premature adipocyte 49.3±11.3, mature adipocyte 110.0±4.6 pg/mL (ELISA). PAI-1 mRNA levels were increased in mature adipocyte (relative expression to GAPDH: MSC 314.9±46.5, premature adipocyte 215.1, mature adipocyte 3766.1±656.2). Since PPARÿ activation is known to promote maturation and re-generation of fat-derived adipocytes, we next examined the potential of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) on the BM adipocytes, leptin and PAI-1 production and the survival of the leukemic cells. CDDO induced adipocyte re-generation with significant increase of the number of Oil-Red(+) small sized lipid vesicles without apoptosis induction. This resulted in a markedly enhanced leptin release from adipocytes (10-fold and 23-fold increase at 0.5 μM and 1.0 μM CDDO, respectively, at 72 hrs) without change in leptin mRNA transcription. On the contrary, PAI-1 mRNA levels were significantly decreased by CDDO (6 fold decrease in MSC, 4 fold decrease in premature adipocyte, 6 fold decrease in mature adipocyte). Co-culture of U937 cells with CDDO-primed premature adipocytes and mature adipocytes resulted in increased spontaneous apoptosis of U937 cells compared to adipocytes not exposed to CDDO (% specific apoptosis, U937 co-cultured with CDDO-primed premature adipocytes 26.9 %, mature adipocytes 20.9 %). At the same time, CDDO-primed premature adipocytes induced significant cell cycle progression with decreased proportion of G0/G1-phase and increase in S-phase fractions in U937 cells (Table 2). Co-culture with CDDO-primed premature adipocytes or with premature adipocytes co-treated with recombinant leptin increased subG1- and S-phase fractions in Ara-C-treated U937 cells compared to U937 cells co-cultured with premature adipocytes (Table 3). In mature adipocytes, which already produce high levels of leptin, CDDO or leptin treatment failed to modulate anti-apoptotic or proliferative effects of AraC on U937 cells. In contrast, human recombinant PAI-1 effectively inhibited spontaneous and Ara-C induced apoptosis of U937 cells (decreased % of Annexin V: spontaneous apoptosis 11.2±1.1%, Ara-C induced apoptosis 15.1± 1.7%). In summary, these results suggest that BM pre-adipocytes support proliferation and survival of myeloid leukemia cells in part through complementary effects of leptin and PAI-1. Our findings indicate that secretion of leptin during MSC differentiation or through PPARg ligation promotes cell cycle progression, while PAI-1 primarily inhibits apoptosis of AML cells. It is conceivable that increased adipocyte content of BM in elderly AML patients may negatively affect the responsiveness of AML cells to chemotherapy. Disclosures: No relevant conflicts of interest to declare.
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Naveiras, Olaia, Valentina Nardi, Parul Sharma, Peter Hauschka, and George Q. Daley. "Bone Marrow Adipocytes: A Novel Negative Regulator of the Hematopoietic Microenvironment." Blood 110, no. 11 (November 16, 2007): 1405. http://dx.doi.org/10.1182/blood.v110.11.1405.1405.
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Abstract In the bone marrow (BM), osteoblasts and endothelium constitute functional niches providing positive or negative signals for hematopoietic stem cell (HSC) self-renewal. In addition to hematopoietic cells, endothelial cells, and osteoblasts, adult BM contains numerous adipocytes. Interestingly, the number of adipocytes correlates inversely with the gross hematopoietic activity of the marrow. Whether adipocytes have a direct effect on hematopoietic progenitors or whether they act as mere space-fillers in this context remains unclear. To determine the potential role of bone marrow adipocytes in hematopoiesis, we induced bone marrow-derived OP9 mesenchymal cells to differentiate into either osteoblastic or adipocytic stroma, and then tested their capacity to serve as surrogate HSC niches during in vitro hematopoietic culture in the absence of exogenous growth factors. We found that the presence of BM-derived adipocytes suppresses the expansion of short-term hematopoietic progenitors by at least two fold, as measured by the number of CD45+ cells expanded, the number of colony forming unit cells (CFU-Cs) and the competitive repopulation units (CRUs) during the first two months post-transplant. As an in vivo correlate, we compared the hematopoietic activity within the BM of the adipocyte-poor thoracic vertebrae and the adipocyte-rich proximal tail vertebrae. Indeed, we found that the percentage of HSCs (ckit+Lin-Sca1+), CMPs, GMPs and MEPs was decreased by two fold in the adipocyte-rich BM as determined phenotypically by FACS and functionally by short-term and long-term competitive repopulation assays. Mechanistically, oligonucleotide expression microarrays and conditioned media experiments on the OP9 co-cultures suggest that the inhibition of the progenitor compartment in adipocyte-rich environments is due to the loss of supportive factors (Notch ligands, N-cadherin, Angiopoietin-1, SCF, BMPs and Wnt5a) in addition to the presence of an active inhibitor. Finally, we found bone marrow adipocytes to accumulate in great numbers upon bone marrow ablation, a process that is hindered in genetically adipocyte-deficient mice. Since early BM transplant survival depends on the rapid accumulation of short term hematopoietic progenitors, whose replication we found hindered in adipocyte-rich BM, we were interested to explore whether the absence of adipocytes in the context of BM transplantation would foster faster recovery of lethally irradiated mice. As predicted, circulating leukocyte counts on the third week post-transplant were 3–5 times higher on the recovering fatless mice. Accordingly, the percentage of CFU-Cs, HSCs, CMPs, GMPs and MEPs on day 17 post-transplant was doubled on the adipocyte-depleted mice as compared to their wildtype littermates. We therefore conclude that, as seen in vitro, the presence of adipocytes in the recovering HSC niche is detrimental to the rapid hematopoietic expansion required to reconstitute blood production. We are currently examining the pharmacologic modulation of adipocyte formation for its effects in BM transplantation.
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Horowitz, Mark C., Ryan Berry, Brandon Holtrup, Zachary Sebo, Tracy Nelson, Jackie A. Fretz, Dieter Lindskog, et al. "Bone marrow adipocytes." Adipocyte 6, no. 3 (July 3, 2017): 193–204. http://dx.doi.org/10.1080/21623945.2017.1367881.
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Kastrenopoulou, Afroditi, Kyriakos E. Kypreos, Nicholaos I. Papachristou, Stavros Georgopoulos, Ioulia Mastora, Ioanna Papadimitriou-Olivgeri, Argyro Spentzopoulou, et al. "ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice." International Journal of Molecular Sciences 23, no. 9 (April 27, 2022): 4834. http://dx.doi.org/10.3390/ijms23094834.
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In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display a bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, and Pgc1a; and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice, adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, using flow cytometry we found that the elevated adiposity in the ApoA1 knockout mice is associated with a significant reduction in the compartments of hematopoietic stem cells and common myeloid, but not of the common lymphoid, progenitors. Moreover, the ‘beiging’-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1—and most probably HDL-C—regulate bone marrow microenvironment, favoring beige/brown adipocyte characteristics.
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Philchenkov, A. A. "Bone marrow adipocytes and multiple myeloma." Oncohematology 14, no. 1 (April 10, 2019): 60–75. http://dx.doi.org/10.17650/1818-8346-2019-14-1-60-75.
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Multiple myeloma originating from clonal proliferation of plasma cells in the bone marrow is one of the most prevalent hematological malignancies worldwide. The pathogenetic mechanisms of multiple myeloma are far from being elucidated. Nevertheless, it is known that the adipocytes as the prevalent cellular component of bone marrow microenvironment contribute significantly to multiple myeloma growth and progression. The review discloses the recent data on the interactions between bone marrow adipocytes and myeloma cells, hematopoietic stemcells, hematopoietic progenitor cells, mesenchimal stem cells, osteoblasts, osteoclasts, endothelial cells, and cells of immune system. Also, the review places special emphasis on bone marrow adipocyte-produced adipokines, growth factors, cytokines, chemokines, and fatty acids providing the conditions for the preferential growth and migration of malignant plasma cells and contributing to hematopoiesis supression, bone tissue resorption, angiogenesis activation and immunosuppression.
Dissertations / Theses on the topic "Bone marrow adipocytes"
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MATTIUCCI, DOMENICO. "The regulation of haematopoietic niche: is there a role for Bone Marrow Adipocytes?" Doctoral thesis, Università Politecnica delle Marche, 2019. http://hdl.handle.net/11566/263669.
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Il midollo osseo (BM) è un microambiente altamente specializzato che fornisce supporto trofico e strutturale attraverso le sue componenti stromali alle cellule staminali emopoietiche (HSC). Gli adipociti midollari (BM-A) costituiscono la componente stromale più abbondante nella nicchia, tuttavia il loro ruolo nella regolazione dell’emopoiesi non è stato ancora ben definito. È stato tuttavia dimostrato che durante la CR avviene un’espansione del tessuto adiposo midollare, responsabile a sua volta di aumentati livelli di Adiponectina (APN) sierica circolante, un ormone potenzialmente coinvolto nella regolazione dell’emopoiesi.
Gli scopi di questo lavoro sono stati quelli di caratterizzare i BM-A dal punto di vista funzionale e molecolare e di determinare se l’APN possa svolgere un ruolo nella regolazione delle HSC durante la CR.
A questo scopo è stata effettuata un’analisi microarray su BM-A isolati da pazienti che si sottoponevano a chirurgia dell’anca, mentre la caratterizzazione funzionale è stata effettuata tramite co-cultura con HSC. Il ruolo dell’APN è stato studiato utilizzando un modello murino APN-/- e valutando i cambiamenti nelle HSC e nelle cellule ematopoietiche circolanti in topi sottoposti a CR. I dati molecolari hanno mostrato che i BM-A hanno uno specifico pattern di espressione genica diverso dagli adipociti sottocutanei e lo studio funzionale ha dimostrato che essi sono capaci di sostenere la sopravvivenza e la differenziazione delle HSC in coltura.
Lo studio dei topi APN-/- ha inoltre mostrato che in condizioni di CR l’APN svolge un ruolo nella regolazione della granulopoiesi e della linfopoiesi, i topi KO infatti presentavano un maggior numero di granulociti ma un ridotto numero di linfociti circolanti. Questi risultati suggeriscono che i BM-A
possano contribuire alla sopravvivenza delle cellule staminali emopoietiche e che l’APN partecipi alla regolazione dell’emopoiesi normale in condizioni di CR.The bone marrow (BM) niche is a highly specialised microenvironment that provides structural and trophic support through its stromal components for Haematopoietic Stem Cells (HSC). Adipocytes (BM-A) are the most abundant stromal components in the niche, however, their role in haematopoiesis regulation remain unclear. It has been demonstrated that during caloric restriction (CR) there is an expansion of bone marrow adipose tissue and this contributes to increased circulating levels of adiponectin (APN), a hormone potentially involved in haematopoiesis regulation. The aims of our work were to molecularly and functionally characterise BM-A, and to determine if APN contributes to the regulation of the HSC during CR. To address these aims, human BM-A were isolated from hip surgery patients and studied through microarray analysis; while their relationship with HSC was assessed in vitro using long-term co-culture assay with HSC. The role of APN was studied using a mouse model of APN-/- and evaluating the characteristics of HSC and of circulating haematopoietic cells by flow cytometry and by Colony Forming Unit (CFU) assays in mice under CR. Molecular data suggested that BM-A displayed a specific gene expression profile and that they are capable of supporting HSC survival in vitro. Adiponectin KO mouse models showed that KO animals had a reduced number of white blood cells which turned into an increased proportion of Granulocytes in the whole CD45 population and to a significantly reduced number of B cells especially after the first week of CR. These results suggested that BM-A may contribute to the survival of HSC and that APN contributes to the regulation of immune cells during CR.
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Delikat, Sylvie. "Effects of interleukin 1#beta# on human bone marrow stromal cells, with particular relevance to adipocytes." Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359186.
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Tang, Kai Dun. "Dissecting the prostate cancer stem cell niche inside the bone marrow." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/88935/1/Kai%20Dun_Tang_Thesis.pdf.
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Prostate cancer frequently metastasizes to bone, which becomes incurable; yet how cancer cells manage to migrate and grow inside the bone remains unknown. In this study I have discovered that both bone and fat cells within the bone marrow actively promote the survival and expansion of prostate cancer cells, and have subsequently developed approaches that can effectively inhibit these processes. Therefore, my work offers opportunities for the development of new prognostic and therapeutic approaches against metastatic prostate cancer and have the potential for improving the treatment outcome of the patients.
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Paquet, Amélie. "Peptides de l’immunité innée (défensines et cathélicidines) : expression dans les contextes d’obésité et de diabète de type 2, et lien avec la régulation fonctionnelle des adipocytes médullaires et l’os." Electronic Thesis or Diss., Littoral, 2024. https://documents.univ-littoral.fr/access/content/group/50b76a52-4e4b-4ade-a198-f84bc4e1bc3c/BULCO/Th%C3%A8ses/MABLab/123427_PAQUET_2024_archivage.pdf.
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L'obésité est un facteur de risque majeur de diabète de type 2 (DT2), favorisés par une inflammation systémique et une résistance à l'insuline. Ces pathologies métaboliques sont associées à une fragilité osseuse augmentant significativement le risque de fracture souvent sans modification de la masse osseuse. Elles s'accompagnent aussi d'un niveau de graisse dans la moelle osseuse (adiposité médullaire (AM)) anormalement élevé et suspectée de jouer un rôle délétère sur l'os. Cependant, les mécanismes responsables de l'accroissement de l'AM et ses conséquences sur l'os sont encore mal définis. Les défensines et la cathélicidine, des peptides antimicrobiens de l'immunité innée dont l'expression est modifiée dans l'obésité et le DT2, semblent influencer la différenciation ostéoblastique de cellules souches squelettiques (CSS). Cette thèse explore les relations entre l'expression du gène de la cathélicidine, la régulation de l'AM, et les altérations osseuses dans les contextes d'obésité et de DT2. La première partie de ce travail a évalué, dans des modèles murins d'obésité (basé sur un régime riche en lipides, High Fat Diet-HFD) et de DT2 (HFD associé à un traitement par streptozotocine-STZ), les relations entre l'expression de la cathélicidine murine (CRAMP : cathelicidin-related antimicrobial peptid), l'AM, la microarchitecture et la fragilité osseuse. Les souris C57BL/6J mâles soumises à un régime HFD développent une obésité hyperinsulinémique, caractérisée par un gain de poids, une hyperglycémie modérée, une intolérance au glucose et une insulino-résistance. Cette obésité a induit une réduction de l'épaisseur trabéculaire et corticale du tibia, associée à une expansion significative de l'AM, sans modification des taux circulants du peptide CRAMP malgré une baisse de l'expression de ses transcripts dans le tissu adipeux viscéral (TAV). Ces observations soulignent un effet de l'insuline sur l'accumulation des adipocytes médullaires (AdMeds). En revanche, le modèle HFD/STZ induit une hyperglycémie et une insulinopénie marquées, caractéristiques d'un DT2, limitant l'expansion des graisses périphériques et médullaires par rapport aux souris HFD. Ces souris diabétiques présentent une fragilité osseuse accrue, avec une réduction du nombre de trabécules de tibia et une baisse de rigidité de l'os cortical fémoral, associées à des taux réduits de CRAMP circulant. Cela suggèrent une corrélation entre la diminution de CRAMP circulant dans le DT2 et une qualité osseuse compromise à l'origine de la fragilité osseuse des souris diabétiques. Dans la deuxième partie de cette thèse, nous avons étudié in vitro l'expression du gène de la cathélicidine humaine (CAMP) dans les AdMeds différenciés à partir de CSS, et sa régulation par divers stimuli métaboliques. Pour la première fois, nous avons détecté l'expression des transcrits de CAMP dans les AdMeds dès le jour 3 de différenciation, avec une augmentation linéaire jusqu'à maturité des AdMeds au jour 21. En présence de fortes concentrations de glucose (11 ou 25 mM), le taux d'ARNm de CAMP est significativement réduit dans les AdMeds, ce qui corrobore la corrélation négative observée entre CRAMP circulant et la glycémie des souris diabétiques. En outre, le traitement des AdMeds différenciés avec du butyrate ou de l'oléate a entraîné une augmentation des ARNm de CAMP, tandis que le propionate a induit un effet inverse. Ces régulations suggèrent que les taux altérés d'acides gras libres dans les contextes d'obésité/DT2 ou de fragilité osseuse peuvent impacter la sécrétion de CAMP dans le plasma et la moelle osseuse. Ce travail de thèse suggère que l'expression systémique de CAMP pourrait constituer un marqueur immuno-métabolique de la fragilité osseuse associée au DT2. D'autres études sont nécessaires pour préciser les mécanismes régulant l'expression de la cathélicidine en contextes d'obésité et de DT2 et mieux comprendre son rôle dans la régulation de l'AM et de la qualité osseuseObesity is a major risk factor for developing type 2 diabetes (T2D), the diseases favoured by systemic inflammation and insulin resistance. These metabolic diseases are associated to bone fragility increasing significantly the risk of fracture, often without modification in bone mineral density. Obesity and T2D are also accompanied by an abnormal high level of fat in the bone marrow (bone marrow adiposity (BMA)) which is suspected to exert a deleterious effect on the bone. However, the underlying mechanisms increasing the BMA and its consequences on bone tissue are not fully understood. The defensins and the cathelicidin, the antimicrobial peptides of the innate immunity the expression of which is modified in obesity and T2D, seem to influence the osteoblastic differentiation of skeletal stem cells (SSC). This PhD thesis explores the relationships between the expression of the cathelicidin gene, the regulation of BMA, and the bone alterations in the context of obesity and T2D. The first part of this work evaluated, in murine models of obesity -based on High Fat Diet - HFD) and of T2D (induced by HFD combined with streptozotocin-STZ treatment), the relations between the expression of the murine cathelicidin (CRAMP : cathelicidin-related antimicrobial peptide), the BMA, and bone microarchitecture and fragility. C57BL/6J male mice fed with HFD have developed hyperinsulinemic obesity, characterized by weight gain, a moderate hyperglycaemia, an impaired glucose tolerance with an insulin resistance. This obesity induced decreased trabecular and cortical thickness of the tibia, associated with a significant expansion of BMA, without changes in the circulating levels of the CRAMP peptide despite a decreased expression of its transcripts in visceral adipose tissue (VAT). These findings highlight the role of insulin in the accumulation of bone marrow adipocytes (BMAds). In contrast, the HFD/STZ mice model induces a marked hyperghycemia and insulinopenia, features of T2D, limiting the expansion of both peripheral and marrow fat as compared to the HFD group. The HFD/STZ diabetic mice also exhibit increased bone fragility, as characterized by a reduction in the trabeculae number of the tibia and a decrease of cortical rigidity of the femur, associated with decreased of CRAMP circulating levels. These alterations suggest a correlation between declined serum levels of CRAMP with a compromised bone quality leading to the bone fragility in diabetic mice. In the second part of this thesis, we studied in vitro the expression of the human cathelicidin gene (CAMP) in BMAds differentiated from SSC, as well as its regulation in response to various metabolic stimuli. For the first time to our knowledge, this study detected the expression of CAMP transripts in BMAds as early as the third day of differentiation, with a gradual increase until mature adipocytes on day 21. Under high glucose concentration (11 or 25 mM), the mRNA levels of CAMP are significantly reduced in BMAds, thus corroborating the negative correlation observed between circulating CRAMP and glycaemia in diabetic mice. Furthermore, treatment of differentiated BMAds with butyrate or oleate led to an increase in CAMP transcripts, whereas propionate caused an opposite effect on CAMP expression in vitro. These regulations suggest that abnormal levels of free fatty acids in the contexts of obesity and T2D or of bone fragility, may have effects on plasma and bone marrow levels of CAMP. Although further studies are needed, this thesis work suggests that the systemic expression of CAMP could constitute an immune-metabolic marker of bone fragility related to T2D. Future research is essential to clarify the mechanisms regulating the cathelicidin expression and better understand its role in the regulation of BMA and bone quality in the contexts of obesity and T2D
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Mukohira, Hisa. "Mesenchymal stromal cells in bone marrow express adiponectin and are efficiently targeted by an adiponectin promoter-driven Cre transgene." Kyoto University, 2020. http://hdl.handle.net/2433/253155.
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Mareddy, Shobha R. "Characterization of bone marrow stromal clonal populations derived from osteoarthritis patients." Thesis, Queensland University of Technology, 2008. https://eprints.qut.edu.au/17151/1/Shobha_Reddy_Mareddy_Thesis.pdf.
Full textAbstract:
This work is concerned with the characterization of mesenchymal stem cells (MSC) specifically from bone marrow samples derived from patients with osteoarthritis (OA). The multilineage potential of mesenchymal stem cells as well as their ease of exvivo expansion makes these cells an attractive therapeutic tool for applications such as autologous transplantation and tissue engineering. Bone marrow is considered a source of MSC. However, there is a general assumption that the occurrence of MSCs and their activity in bone marrow diminishes with age and disease. This prompted us to isolate and identify multipotential and self-renewing cells from patients with the degenerative disease osteoarthritis, with the view of using these cells for autologous cell therapies. It is therefore of great potential benefit to investigate the isolation and characterization of stem cell/progenitors from bone marrow samples of patients with osteoarthritis in greater detail. We employed a single cell clone culture method in order to develop clonal cell populations from three bone marrow samples and characterized them based on their proliferation and differentiation capabilities. The clonal populations were grouped into fast-growing and slow-growing clones based on their proliferation rates. The fastgrowing clones displayed 20-30% greater proliferation rate than the slow-growing clones. The study also revealed that the proliferation rates were directly proportional to their differentiation capacities. Most of the fast-growing clones were found to be tripotential for osteogenic, chondrogenic and adipogenic lineages, whereas the slow growing clones were either uni or bipotential. Flow cytometry analysis for the phenotype determination using putative MSC surface markers did not reveal any difference between the two clonal populations indicating a need for further molecular studies. Two approaches were employed to further investigate the molecular processes involved in the existence of such varying populations. In the first method gene expression studies were performed between the fast-growing (n=3) and slow-growing (n=3) clonal populations to identify potential genetic markers associated with cell 'sternness' using the Stem Cell RT2 ProfilerTM PCR Array comprising a series of 84 genes related to stem cell pathways. Ten genes were identified to be commonly and significantly over represented in the fast-growing stem cell clones when compared to slow-growing clones. This included expression of transcripts beyond MSC lineage specification such as SOX2, NOTCH1 and FOXA2 which signified that stem cell maintenance requires a coordinated regulation by multiple signalling pathways. The second study involved an extensive protein expression profiling of the fast growing (n=2) and slow growing (n=2) clonal populations using off-line Two Dimensional Liquid Chromatography (2D-LC)/Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry (MS). A total of 67 proteins were identified, of which 11 were expressed at significantly different levels between the subpopulations. Protein ontology revealed these proteins to be associated with cellular organization, cytokinesis, signal transduction, energy pathways and cell stress response. Of particular interest was the differential presentation of the proteins calmodulin, tropomyosin and caldesmon between fast- and slow-growing clones. Based on their reported roles in the regulation of cell proliferation and maintenance of cell integrity, we draw an association between their expression and the altered status in which the subpopulations exist. Based on our observations, these proteins may be prospective molecular markers to distinguish between the fast-growing and slow-growing subpopulations. In summary, this study demonstrated the existence of potential stem cells of therapeutic importance in spite of a supposedly smaller stem cell compartment in patients with osteoarthritis. Furthermore, the differentially expressed genes between the sub-populations highlight the 'sternness' of the potential clones, an observation supported by the expression of proteins which act as effective modulators in the maintenance of cell integrity and cell cycle regulation. This study provides a basis for more detailed investigations in search of selective cell surface markers
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Mareddy, Shobha R. "Characterization of bone marrow stromal clonal populations derived from osteoarthritis patients." Queensland University of Technology, 2008. http://eprints.qut.edu.au/17151/.
Full textAbstract:
This work is concerned with the characterization of mesenchymal stem cells (MSC) specifically from bone marrow samples derived from patients with osteoarthritis (OA). The multilineage potential of mesenchymal stem cells as well as their ease of exvivo expansion makes these cells an attractive therapeutic tool for applications such as autologous transplantation and tissue engineering. Bone marrow is considered a source of MSC. However, there is a general assumption that the occurrence of MSCs and their activity in bone marrow diminishes with age and disease. This prompted us to isolate and identify multipotential and self-renewing cells from patients with the degenerative disease osteoarthritis, with the view of using these cells for autologous cell therapies. It is therefore of great potential benefit to investigate the isolation and characterization of stem cell/progenitors from bone marrow samples of patients with osteoarthritis in greater detail. We employed a single cell clone culture method in order to develop clonal cell populations from three bone marrow samples and characterized them based on their proliferation and differentiation capabilities. The clonal populations were grouped into fast-growing and slow-growing clones based on their proliferation rates. The fastgrowing clones displayed 20-30% greater proliferation rate than the slow-growing clones. The study also revealed that the proliferation rates were directly proportional to their differentiation capacities. Most of the fast-growing clones were found to be tripotential for osteogenic, chondrogenic and adipogenic lineages, whereas the slow growing clones were either uni or bipotential. Flow cytometry analysis for the phenotype determination using putative MSC surface markers did not reveal any difference between the two clonal populations indicating a need for further molecular studies. Two approaches were employed to further investigate the molecular processes involved in the existence of such varying populations. In the first method gene expression studies were performed between the fast-growing (n=3) and slow-growing (n=3) clonal populations to identify potential genetic markers associated with cell 'sternness' using the Stem Cell RT2 ProfilerTM PCR Array comprising a series of 84 genes related to stem cell pathways. Ten genes were identified to be commonly and significantly over represented in the fast-growing stem cell clones when compared to slow-growing clones. This included expression of transcripts beyond MSC lineage specification such as SOX2, NOTCH1 and FOXA2 which signified that stem cell maintenance requires a coordinated regulation by multiple signalling pathways. The second study involved an extensive protein expression profiling of the fast growing (n=2) and slow growing (n=2) clonal populations using off-line Two Dimensional Liquid Chromatography (2D-LC)/Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry (MS). A total of 67 proteins were identified, of which 11 were expressed at significantly different levels between the subpopulations. Protein ontology revealed these proteins to be associated with cellular organization, cytokinesis, signal transduction, energy pathways and cell stress response. Of particular interest was the differential presentation of the proteins calmodulin, tropomyosin and caldesmon between fast- and slow-growing clones. Based on their reported roles in the regulation of cell proliferation and maintenance of cell integrity, we draw an association between their expression and the altered status in which the subpopulations exist. Based on our observations, these proteins may be prospective molecular markers to distinguish between the fast-growing and slow-growing subpopulations. In summary, this study demonstrated the existence of potential stem cells of therapeutic importance in spite of a supposedly smaller stem cell compartment in patients with osteoarthritis. Furthermore, the differentially expressed genes between the sub-populations highlight the 'sternness' of the potential clones, an observation supported by the expression of proteins which act as effective modulators in the maintenance of cell integrity and cell cycle regulation. This study provides a basis for more detailed investigations in search of selective cell surface markers
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Withers, Catherine Nicole Kaminski. "RAD GTPASE: IDENTIFICATION OF NOVEL REGULATORY MECHANISMS AND A NEW FUNCTION IN MODULATION OF BONE DENSITY AND MARROW ADIPOSITY." UKnowledge, 2017. http://uknowledge.uky.edu/biochem_etds/34.
Full textAbstract:
The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates voltage-dependent calcium channel function. Given its expression in both excitable and non-excitable cell types, the control mechanisms for Rad regulation and the potential for novel functions for Rad beyond calcium channel modulation are open questions. Here we report a novel interaction between Rad and Enigma, a scaffolding protein that also binds to the E3 ubiquitin ligase Smad ubiquitin regulatory factor 1 (Smurf1). Overexpression of Smurf1, but not of a catalytically inactive mutant enzyme, results in ubiquitination of Rad and down regulation of Rad protein levels. The Smurf1-mediated decrease in Rad levels is sensitive to proteasome inhibition and requires the ubiquitination site Lys204, suggesting that Smurf1 targets Rad for degradation. Rad protein levels, but notably not mRNA levels, are increased in the hearts of Enigma-/- mice, leading to the hypothesis that Enigma may function as a scaffold to enhance Smurf1 regulation of Rad.
In addition to ubiquitination, phosphorylation of RGK proteins represents another potential means of regulation. Indeed, Rem phosphorylation has been shown to abolish calcium channel inhibition. We demonstrate that b-adrenergic signaling promotes Rad phosphorylation at Ser39. Rad Ser39 phosphorylation is correlated with a decrease in the interaction between Rad and the CaVb subunit of the calcium channel and an increase in Rad binding to 14-3-3. Interestingly, Enigma overexpression promotes an increase in Rad Ser39 phosphorylation as well. Despite an interaction between Enigma and the CaV1.2 calcium channel subunit, overexpression of Enigma had no effect on Rad-mediated channel inhibition. Thus, Rad Ser39 phosphorylation alters its association with the calcium channel, but its impact on calcium channel regulation has yet to be determined.
Finally, we report a novel function for Rad in the regulation of bone homeostasis. Rad deletion in mice results in a significant decrease in bone mass. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed in the absence of Rad. Microarray analysis revealed that canonical osteogenic gene expression is not altered in Rad-/- osteoblasts; instead robust up-regulation of matrix Gla protein (MGP, +11-fold), an inhibitor of mineralization and a protein secreted during adipocyte differentiation, was observed. Strikingly, Rad deficiency also resulted in significantly higher bone marrow adipose tissue (BMAT) levels in vivo and promoted spontaneous in vitro adipogenesis of primary calvarial osteoblasts. Adipogenic differentiation of WT osteoblasts resulted in the loss of endogenous Rad protein, further supporting a role for Rad in the control of BMAT levels. These findings reveal a novel in vivo function for Rad signaling in the complex physiological control of skeletal homeostasis and bone marrow adiposity.
In summary, this dissertation expands our understanding of Rad regulation through identification of a novel binding partner and characterization of post-translational regulatory mechanisms for Rad function. This work also defines a new role for Rad that may not depend upon its calcium channel regulatory properties: regulation of the bone-fat balance. These findings suggest that the regulation of Rad GTPase is likely more complex than guanine nucleotide cycling and that functions of Rad in non-excitable tissues warrant further study.
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Anastassiadis, Konstantinos, and Maria Rostovskaya. "Differential Expression of Surface Markers in Mouse Bone Marrow Mesenchymal Stromal Cell Subpopulations with Distinct Lineage Commitment." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-191602.
Full textAbstract:
Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.
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Anastassiadis, Konstantinos, and Maria Rostovskaya. "Differential Expression of Surface Markers in Mouse Bone Marrow Mesenchymal Stromal Cell Subpopulations with Distinct Lineage Commitment." Public Library of Science, 2012. https://tud.qucosa.de/id/qucosa%3A29135.
Full textAbstract:
Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.
Book chapters on the topic "Bone marrow adipocytes"
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Strauchen, James A. "Disorders of Bone Marrow Stroma." In Diagnostic Histopathology of the Bone Marrow, 307–12. Oxford University PressNew York, NY, 1996. http://dx.doi.org/10.1093/oso/9780195097566.003.0029.
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Abstract The bone marrow stroma consists of the supporting cells of the bone marrow, the bone marrow blood vessels and sinusoids, and the adipocytes. These elements may be involved in a variety of hematologic and nonhematologic disorders affecting the bone marrow. The disorders considered in this chapter include bone marrow infarction, vasculitis, and serous fat atrophy. Bone marrow infarction refers to coagulative necrosis of bone marrow elements. Bone marrow infarction occurs most frequently as a complication of neoplasms involving the bone marrow (Kiraly and Whelby, 1976), but is also seen occasionally in vasoocclusive disorders and hemoglobinopathies (sickle cell disease or hemoglobin SC disease). Bone marrow necrosis in hematologic neoplasms occurs most frequently in association with acute lymphocytic leukemia (Navari et al, 1983) and bone marrow necrosis may be the presenting manifestation of acute lymphocytic leukemia (Niebrugge and Benjamin, 1983). Patients with bone marrow necrosis frequently present with bone pain and fever.
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Strauchen, James A. "The Normal Bone Marrow." In Diagnostic Histopathology of the Bone Marrow, 10–19. Oxford University PressNew York, NY, 1996. http://dx.doi.org/10.1093/oso/9780195097566.003.0002.
Full textAbstract:
Abstract The bone marrow is the major site of postnatal hematopoiesis. The bone marrow contains stromal elements (endothelial cells, fibroblast-like cells, adipocytes, macrophages), hematopoietic elements (stem cells, granulocytes, erythroid cells, megakaryocytes), and other elements (lymphocytes, plasma cells, and mast cells). Hematopoiesis is regulated and sustained by a complex cellular interaction of hematopoietic and stromal elements and a network of cytokine growth factors, including the interleukins (11-1, 11-3, 11-5, 11- 6, 11-7, 11-11, stem cell factor) and colony-stimulating factors (G-CSF, GM-CSF, erythropoietin) (Metcalf, 1989; Dorshkind, 1990). The marrow cellularity indicates the fraction of marrow space occupied by hematopoietic cells. Cellularity is commonly expressed as a percentage (0% cellularity indicating an “empty” or aplastic marrow and 100% indicating a “packed” or full marrow) and determined from the relative proportion of hematopoietic and fat cells. Marrow cellularity is greatly dependent on age. At birth, hematopoietic marrow extends into the appendicular skeleton and cellularity is 100%. In adults, hematopoietic marrow is found only in the axial skeleton (pelvis, vertebrae, ribs, and sternum) and is replaced by fatty marrow at other sites. The cellularity of the posterior iliac crest approximates 50% in adults (50% hematopoietic cells and 50% fat) varying from up to 70% (70% hematopoietic cells and 30% fat) in childhood and adolescence to less than 30% (30% hematopoietic cells and 70% fat) in advanced age (Figs. 2.1 and 2.2).
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Sotoca, Ana M., Michael Weber, and Everardus J. J. van Zoelen. "Gene Expression Regulation underlying Osteo-, Adipo-, and Chondro-Genic Lineage Commitment of Human Mesenchymal Stem Cells." In Medical Advancements in Aging and Regenerative Technologies, 76–94. IGI Global, 2013. http://dx.doi.org/10.4018/978-1-4666-2506-8.ch004.
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Human mesenchymal stem cells have a high potential in regenerative medicine. They can be isolated from a variety of adult tissues, including bone marrow, and can be differentiated into multiple cell types of the mesodermal lineage, including adipocytes, osteocytes, and chondrocytes. Stem cell differentiation is controlled by a process of interacting lineage-specific and multipotent genes. In this chapter, the authors use full genome microarrays to explore gene expression profiles in the process of Osteo-, Adipo-, and Chondro-Genic lineage commitment of human mesenchymal stem cells.
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Li, Chenghai. "Isolation and Expansion of Mesenchymal Stem/Stromal Cells, Functional Assays and Long-Term Culture Associated Alterations of Cellular Properties." In Cell Culture [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.100286.
Full textAbstract:
Mesenchymal stem cell/stromal cells (MSCs) can differentiate into a variety of cell types, including osteocytes, adipocytes and chondrocytes. MSCs are present in the multiple types of adult tissue, such as bone marrow, adipose tissue, and various neonatal birth-associated tissues. Given their self-renewal and differentiation potential, immunomodulatory and paracrine properties, and lacking major histocompatibility complex (MHC) class II molecules, MSCs have attracted much attention for stem cell-based translational medicine research. Due to a very low frequency in different types of tissue, MSCs can be isolated and expanded in vitro to derive sufficient cell numbers prior to the clinical applications. In this chapter, the methodology to obtain primary bone marrow-derived MSCs as well as their in vitro culture expansion will be described. To assess the functional properties, differentiation assays, including osteogenesis, chondrogenesis and adipogenesis, 3-D culture of MSCs and co-culture of MSCs and tumor cells are also provided. Finally, the long-term culture associated alterations of MSCs, such as replicative senescence and spontaneous transformation, will be discussed for better understanding of the use of MSCs at the early stages for safe and effective cell-based therapy.
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Bubnovskaya, L., I. Ganusevich, S. Merentsev, and D. Osinsky. "The Impact of Cancer-associated Adipocytes on Prognostic Value of CD8 and CD45RO T Lymphocytes in Tumor and Bone Marrow and Survival of Patients with Gastric Cancer with Obesity." In Achievements and Challenges of Medicine and Medical Science Vol. 5, 1–19. BP International, 2024. https://doi.org/10.9734/bpi/acmms/v5/2481.
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Beck, GR, CE Camalier, G. Bouloux, L. Peng, NB Khazai, and GE Umpierrez. "Defining the Effects of Thiazolidinediones on Osteoblast and Adipocyte Lineage Differentiation from Human Bone Marrow Stem Cells." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P2–185—P2–185. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part2.p4.p2-185.
Full textConference papers on the topic "Bone marrow adipocytes"
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Fritton, J. Christopher, Yuki Kawashima, Hui Sun, Yingjie Wu, Wilson Mejia, Hayden W. Courtland, Clifford J. Rosen, and Shoshana Yakar. "Bone Marrow Adipogenesis Is Affected by Insulin-Like Growth Factor-1 Complexes." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206158.
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Fat tissue, which is composed of lipid-filled adipocytes that accumulate during aging, displaces mineralized tissue and reduces the mechanical integrity bone. Bone marrow adipocytes provide stroma for maintenance of mesencymal stem cells (MSC) and reside at sites of bone turnover (i.e., endosteal surfaces where osteoblasts form new bone), potentially influencing cell activity via a paracrine route.
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Coughlin, Thomas R., Matthew Haugh, Muriel Voisin, Evelyn Birmingham, Laoise M. McNamara, and Glen L. Niebur. "Primary Cilia Knockdown Reduces the Number of Stromal Cells in Three Dimensional Ex Vivo Culture." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14723.
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Mesenchymal stem cells (MSCs) are multipotent stromal cells that reside in the bone marrow and differentiate into connective cell lines, such as adipocytes and osteoblasts [1]. An appropriate balance of MSC differentiation toward adipocytes and osteoblasts is vital to bone homeostasis [6]. In vitro work demonstrates that differentiation of MSCs is influenced by mechanical stimuli [2, 3]. In a mouse model, the ratio of adipocytes to MSCs in the marrow was 19% lower compared to controls following treatment by low magnitude mechanical signals (LMMS) [4]. In mice, LMMS increased MSC number by 46% and the differentiation capacity of MSCs was biased towards osteoblastic compared to adipogenic differentiation [5]. Thus, mechanobiological stimuli may play an important role in maintaining balanced MSC differentiation.
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Herroon, Mackenzie K., Erandi Rajagurubandara, Aimalie L. Hardaway, and Izabela Podgorski. "Abstract B04: Exploring the roles of bone marrow adipocytes in metabolic adaptation of metastatic prostate tumors in bone." In Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; February 26 — March 1, 2014; San Diego, CA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.chtme14-b04.
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Cugno, Chiara, Ganesh Halade, and Md Mizanur Rahman. "Omega-3 fatty acid-rich fish oil supplementation prevents rosiglitazone-induced osteopenia in aging mice." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0099.
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Rosiglitazone is an effective insulin-sensitizer, however, associated with bone loss mainly due to increased bone resorption, and bone marrow adiposity, and decreased bone formation. We investigated the effect of the co-administration of fish oil (FO) rich in omega-3 fatty acids (FAs) on rosiglitazone (RSG)-induced bone loss in aging C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells (MSCs) differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARg/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Our findings demonstrate that fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment. Further clinical studies will be undertaken to establish this treatment regimen for the successful treatment of diabetic patients with rosiglitazone without adverse side effects on bone.
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Ibrahim, Khadega, Chiara Cugno, and Md Mizanur Rahman. "Conjugated Linoleic Acid (CLA) co-treatment alleviates antidiabetic drug, rosiglitazone associated deterioration of bone remodeling." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0148.
Full textAbstract:
Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia due to decreased insulin secretion, defective action or both. The rosiglitazone (RSG) is one of the oral antidiabetic drug used in type 2 (T2) DM and has a unique insulin-sensitizing capacity. However, RSG has a negative side effect on the bone as it stimulates the differentiation of bone marrow-mesenchymal stromal cells (BM-MSCs) into adipocytes at the expense of osteoblasts in the bone marrow microenvironment, disturbing the normal balance of bone remodeling and causing BM adiposity. On the other hand, the trans-10,cis-12 conjugated linoleic acid (CLA), a fatty acid is known as anti-adipogenic, pro-osteogenic. Therefor, this study was designed to assess whether CLA can alleviate the negative effect of RSG on bone. We used adipose tissue derived-mesenchymal stem cells (AT-MSCs) as a human in vitro model to study the effect of CLA, RSG and combined treatment (RSG+CLA) on the osteoblastogenic and adipogenic differentiation of AT-MSCs. Osteoblastogenesis was assessed by Alizarin Red Staining and bone mineralization was assessed by 〖"OsteoImage" 〗^TMassays, whereas adipogenesis was assessed by Oil Red O Staining and LipidTOX assays. Besides, the level of expression of osteogenic and adipogenic markers was measured on treated osteo- and adipo-differentiated MSCs using real time RT-PCR, immunohistochemistry (IHC) and western blot analysis. Compared to RSG group, the combined treatment group stimulates osteoblastogenesis, as evidenced by increased mineralization and upregulation of osteogenic markers OPN and RUNX2 and inhibits adipogenesis in osteogenic media as showed by decreased lipid content and downregulation of adipogenic markers FABP4, LPL and adipsin. In conclusion, the use of CLA as an adjunctive treatment reversed the effects of RSG on osteogenesis and adipogenesis. Further preclinical and clinical studies will be undertaken to establish this treatment regimen for the successful treatment of diabetic patients with rosiglitazone without adverse side effects on bone.
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Liu, Chun, Seungik Baek, and Christina Chan. "The Complementary Effect of Mechanical and Chemical Stimuli on the Neural Differentiation of Mesenchymal Stem Cells." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80131.
Full textAbstract:
Mesenchymal stem cells (MSCs), derived from bone marrow stroma, are a promising source for tissue repair and regeneration, due to their excellent abilities for proliferation and multipotent differentiation. While accumulated evidences during the past decade have shown that MSCs are able to differentiate into osteoblasts, chondrocytes, myoblasts and adipocytes, more recent research suggest their potential in neuronal differentiation [1]. Chemical stimuli, including growth factors, hormones, and other regulatory molecules, are used traditionally to direct MSC differentiation. Our group has previously shown that the intracellular second messenger, cAMP, is able to initiate early phase neuron-like morphology changes and late phase neural differentiation in MSCs [2]. Studies using chemical stimuli alone, however, have shown limited success in differentiating MSCs to mature neurons, thereby suggesting other factors are necessary for this process. In recent years, interest has grown on the impact of mechanical stimulation, such as stiffness, surface topography, and mechanical stretching, on cell fate decision [3].
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Diedrich, Jonathan, Erandi Rajagurubandara, Mackenzie Herroon, and Izabela Podgorski. "Abstract LB-315: Bone marrow adipocytes alter the metabolic phenotype of metastatic prostate cancer cells through the activation of HIF-1a." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-lb-315.
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Van Dyke, William S., Ozan Akkus, and Eric Nauman. "Murine Osteochondral Stem Cells Express Collagen Type I More Strongly on PDMS Substrates Than on Tissue Culture Plastic." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14272.
Full textAbstract:
The discovery of the multipotent lineage of mesenchymal stem cells has dawned a new age in tissue engineering, where an autologous cell-seeded scaffold can be implanted into different therapeutic sites. Mesenchymal stem cells have been reported to differentiate into numerous anchorage-dependent cell phenotypes, including neurons, adipocytes, myoblasts, chondrocytes, tenocytes, and osteoblasts. A seminal work detailing that mesenchymal stem cells can be directed towards differentiation of different cell types by substrate stiffness alone [1] has led to numerous studies attempting to understand how cells can sense the stiffness of their substrate [2–3] Substrate stiffness has been shown to be an inducer of stem cell differentiation. MSCs on extremely soft substrates (250 Pa), similar to the stiffness of bone marrow, became quiescent but still retained their multipotency [4]. Elastic substrates in the stiffness range of 34 kPa revealed MSCs with osteoblast morphology, and osteocalcin along with other osteoblast markers were expressed [1]. However, osteogenesis has been found to increase on much stiffer (20–80 kPa) [5–6] (400 kPa) [7] as well as much softer substrates (75 Pa) [8]. Overall, cells have increased projected cell area and proliferation on stiffer substrates, leading to higher stress fiber formation. This study seeks to understand if the stiffness of the substrate has any effect on the differentiation potential of osteochondral progenitor cells into bone cells, using an in vitro dual fluorescent mouse model.
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Shafat, Manar, Thomas Oellerich, Sebastian Mohr, Stephen Robinson, Dylan Edwards, Rachel Piddock, Amina Abdul-Aziz, et al. "Abstract 4327: Bone marrow adipocytes drive transcriptional changes in leukemic blasts to enhance their capacity to derive energy from free fatty acid metabolism." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-4327.
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Grubač, Siniša, Marko Cincović, Jože Starič, Marinković Došenović, Biljana Delić-Vujanović, and Jasna Prodanov-Radulović. "The relationship of the metabolism of iron, organic matter and phlebotomy with the erythropoiesis of ruminants." In Zbornik radova 26. medunarodni kongres Mediteranske federacije za zdravlje i produkciju preživara - FeMeSPRum. Poljoprivredni fakultet Novi Sad, 2024. http://dx.doi.org/10.5937/femesprumns24012g.
Full textAbstract:
Erythropesis is the process of making red blood cells and it is related to numerous factors in the body. Iron is important because of its role in the process of making hemoglobin. In addition to the mentioned iron, it is an indirect indicator of inflammation and is regulated at the systemic and cellular level, so its lack speaks of the overall health status of individuals. Fe deficiency in the body takes place through three phases. In the first phase, there is emptying of tissue depots, but its total amount in the circulation increases, then follows the second phase or the phase of real deficit with decreasing concentration of serum iron and hemoglobin, and the third phase is the phase in which the significance of iron deficit is clinically seen. Iron deficiency disrupts all aspects of erythropoiesis. Therefore, first the iron reserves are used up, then with the decrease of transported iron, erythropoiesis changes, and when the availability of this iron is completely reduced, anemia will occur due to iron deficiency. Lipid metabolism also plays a very important role in the functioning of hematopoietic stem cells. Fatty acid oxidation is the main catabolic pathway by which energy is produced in hematopoietic stem cells. Long-chain fatty acids are activated in the cytosol and transported to the mitochondria by the transport system. In them, beta oxidation takes place through several known stages, creating acetyl coenzyme A, which starts the cycle of tricarboxylic acids. Deletion of the gene for regulation of fatty acid oxidation causes hematopoiesis stem cells to lose their potential to reconstruct and maintain themselves. Due to the importance of lipolysis in ruminants and the fact that stem cells are found in the lipidrich niches of bone marrow, we will also consider the relationship between bone marrow adipocytes and hematopoiesis. Chronic phlebotomy in rams or Fe deficiency due to inflammation and fatty liver in cows lead to specific changes in red blood cell and blood metabolites. All of the above shows that it is necessary to know the metabolic flows in order to better understand erythropoiesis in ruminants.