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1

Aronson, J., X. C. Shen, R. A. Skinner, W. R. Hogue, T. M. Badger, and C. K. Lumpkin. "Rat model of distraction osteogenesis." Journal of Orthopaedic Research 15, no. 2 (March 1997): 221–26. http://dx.doi.org/10.1002/jor.1100150210.

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2

Fang, Tony D., Randall Nacamuli, HanJoon Song, Kenton Fong, Stephen Warren, and Michael T. Longaker. "Guided tissue regeneration enhances osteogenesis in a rat mandibular distraction osteogenesis model." Journal of the American College of Surgeons 199, no. 3 (September 2004): 49. http://dx.doi.org/10.1016/j.jamcollsurg.2004.05.097.

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3

Sun, Yuxin, Liangliang Xu, Shuo Huang, Yonghui Hou, Yang Liu, Kai-Ming Chan, Xiao-Hua Pan, and Gang Li. "mir-21 Overexpressing Mesenchymal Stem Cells Accelerate Fracture Healing in a Rat Closed Femur Fracture Model." BioMed Research International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/412327.

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MicroRNAs are small noncoding RNAs involved in numerous biological processes. Emerging pieces of evidence suggest that microRNAs play important roles in osteogenesis and skeletal homeostasis. Recent studies indicated the significant regulation function of mir-21 in osteogenesisin vitro, but little information is known about its veritable functionsin vivo. In the present study, we aimed to investigate the effect of mir-21 intervention on osteogenic differentiation of rats bone marrow derived mesenchymal stem cells (rBMSCs) and repair capacity in rats closed femur fracture model with internal fixation. The results showed that the upregulation of mir-21 not only increased the expression of osteopontin and alkaline phosphatase in rBMSCs but also promoted mineralization in the condition of osteogenic induction. Furthermore, the bone healing properties were also improved in fracture healing model according to the results of micro-CT, mechanical test, and histological analysis. The current study confirms that the overexpression of mir-21 could promote osteogenesis and accelerate bone fracture healing, which may contribute to a new therapeutic way for fracture repair.
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4

Kawai, Gou, Takatoshi Ohno, Tomoko Kawaguchi, Akihito Nagano, Mitsuru Saito, Iori Takigami, Aya Matsuhashi, et al. "Human Dental Pulp Facilitates Bone Regeneration in a Rat Bone Defect Model." Bone and Tissue Regeneration Insights 4 (January 2013): BTRI.S10687. http://dx.doi.org/10.4137/btri.s10687.

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The objective of this work was to investigate the osteogenetic ability of the human dental pulp stem cells (hDPSCs) derived from human third molars. We induced alkaline phosphatase (ALP) activity and bone morphogenetic protein 2 (BMP-2) mRNA expression, the markers for bone formation, in hDPSCs by using osteoinductive factors. The implantation of hDPSCs with collagen sponge promoted osteogenesis and fracture healing in the femur of an immunocompromised rat, which was a bone defect model for pseudoarthrosis. Histological analyses revealed that after implantation of the hDPSCs, the size and number of osteoblasts and the rates of osteoid production and mineralization increased to an appreciable extent, whereas the rate of bone resorption decreased. We believe that hDPSC implantation is a simple and safe procedure that can be beneficial in bone regeneration therapy in clinical practice.
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5

Glowacki, J., A. J. M. Schulten, D. Perrott, and L. B. Kaban. "Nicotine impairs distraction osteogenesis in the rat mandible." International Journal of Oral and Maxillofacial Surgery 37, no. 2 (February 2008): 156–61. http://dx.doi.org/10.1016/j.ijom.2007.08.001.

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6

Aronson, J., X. C. Shen, G. G. Gao, F. Miller, T. Quattlebaum, R. A. Skinner, T. M. Badger, and C. K. Lumpkin. "Sustained proliferation accompanies distraction osteogenesis in the rat." Journal of Orthopaedic Research 15, no. 4 (July 1997): 563–69. http://dx.doi.org/10.1002/jor.1100150412.

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7

Yamanaka, Masahiro, Izumi Yoshioka, Manabu Habu, and Kazuhiro Tominaga. "Expression of Smads in Distraction Osteogenesis of Rat Mandibles." Journal of the Kyushu Dental Society 63, no. 5.6 (2010): 268–76. http://dx.doi.org/10.2504/kds.63.268.

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8

Sun, Ruinan, Shuyu Xu, and Zuolin Wang. "Rat sinus mucosa‐ and periosteum‐derived exosomes accelerate osteogenesis." Journal of Cellular Physiology 234, no. 12 (May 9, 2019): 21947–61. http://dx.doi.org/10.1002/jcp.28758.

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9

De Togni, P., H. Niman, V. Raymond, P. Sawchenko, and I. M. Verma. "Detection of fos protein during osteogenesis by monoclonal antibodies." Molecular and Cellular Biology 8, no. 5 (May 1988): 2251–56. http://dx.doi.org/10.1128/mcb.8.5.2251.

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We have generated monoclonal antibodies by using a synthetic peptide corresponding to amino acid positions 4 to 17 of the human fos protein. The antibodies detected both v- and c-fos proteins by immunoprecipitation, immunoblotting, and indirect immunofluorescence. The monoclonal antibodies not only identified the fos protein complex with the cellular 39-kilodalton protein, but also recognized the modified forms of the mouse, rat, and human fos proteins. In day-17 rat embryos, nuclear-staining fos protein could be identified in the cartilage by immunohistochemical staining.
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10

De Togni, P., H. Niman, V. Raymond, P. Sawchenko, and I. M. Verma. "Detection of fos protein during osteogenesis by monoclonal antibodies." Molecular and Cellular Biology 8, no. 5 (May 1988): 2251–56. http://dx.doi.org/10.1128/mcb.8.5.2251-2256.1988.

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We have generated monoclonal antibodies by using a synthetic peptide corresponding to amino acid positions 4 to 17 of the human fos protein. The antibodies detected both v- and c-fos proteins by immunoprecipitation, immunoblotting, and indirect immunofluorescence. The monoclonal antibodies not only identified the fos protein complex with the cellular 39-kilodalton protein, but also recognized the modified forms of the mouse, rat, and human fos proteins. In day-17 rat embryos, nuclear-staining fos protein could be identified in the cartilage by immunohistochemical staining.
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11

Zaminy, Arash, Iraj Ragerdi Kashani, Mohammad Barbarestani, Azim Hedayatpour, Reza Mahmoudi, Safoura Vardasbi, and Mohammad Ali Shokrgozar. "Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells." Indian Journal of Plastic Surgery 41, no. 01 (January 2008): 08–14. http://dx.doi.org/10.1055/s-0039-1699220.

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ABSTRACT Background: Osteogenesis driven by adipose-derived stem cells (ADSCs) is regulated by physiological and pathological factors. Accumulating evidence from in vitro and in vivo experiments suggests that melatonin may have an influence on bone formation. However, little is known about the effects of melatonin on osteogenesis, which thus remains to be elucidated. This study was performed to determine whether melatonin at physiological concentrations (0.01-10 nM) could affect the in vitro proliferation and osteogenic differentiation of rat ADSCs.Materials and Methods: ADSCs were isolated from the fat of adult rats. After cell expansion in culture media and through three passages, osteogenesis was induced in a monolayer culture using osteogenic medium with or without melatonin at physiological concentrations (0.01-10 nM). After four weeks, the cultures were examined for mineralization by Alizarin Red S and von Kossa staining and for alkaline phosphatase (ALP) activity using an ALP kit. Cell viability and apoptosis were also assayed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and flow cytometry, respectively.Results: The results indicated that at physiological concentrations, melatonin suppressed proliferation and differentiation of ADSCs. These data indicate that ADSCs exposed to melatonin, had a lower ALP activity in contrast to the cells exposed to osteogenic medium alone. Similarly, mineral deposition (calcium level) also decreased in the presence of melatonin. Flow cytometry confirmed that cell growth had decreased and that the numbers of apoptotic cells had increased.Conclusion: These results suggest that the physiological concentration of melatonin has a negative effect on ADSC osteogenesis.
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12

Wu, Xiexing, Ziniu Tang, Kang Wu, Yanjie Bai, Xiao Lin, Huilin Yang, Qiang Yang, et al. "Strontium–calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration." Journal of Materials Chemistry B 9, no. 30 (2021): 5982–97. http://dx.doi.org/10.1039/d1tb00439e.

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Sr-CPHC is a starch-reinforced calcium phosphate cement with SrCO3 incorporation, exhibiting synergistic effect of osteogenesis and angiogenesis, which showed a remarkable effect in rat calvarial defect repair.
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13

Lu, Mengmeng, Xiaohua Zhuang, Kaiwei Tang, Peishi Wu, Xiaojing Guo, Linling Yin, Huiliang Cao, and Derong Zou. "Intrinsic Surface Effects of Tantalum and Titanium on Integrin α5β1/ ERK1/2 Pathway-Mediated Osteogenic Differentiation in Rat Bone Mesenchymal Stromal Cells." Cellular Physiology and Biochemistry 51, no. 2 (2018): 589–609. http://dx.doi.org/10.1159/000495280.

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Background/Aims: Accumulating evidence demonstrates the superior osteoinductivity of tantalum (Ta) to that of titanium (Ti); however, the mechanisms underlying these differences are unclear. Thus, the objective of the present study was to examine the effects of Ta and Ti surfaces on osteogenesis using rat bone mesenchymal stromal cells (rBMSCs) as a model. Methods: Ta and Ti substrates were polished to a mirror finish to minimize the influences of structural factors, and the intrinsic surface effects of the two materials on the integrin α5β1/mitogen-activated protein kinases 3 and 1 (ERK1/2) cascade-mediated osteogenesis of rBMSCs were evaluated. Alkaline phosphatase (ALP) activity, Alizarin Red staining, real-time polymerase chain reaction, and western blot assays of critical osteogenic markers were conducted to evaluate the effects of the two substrates on cell osteogenesis. Moreover, the role of the integrin α5β1/ERK1/2 pathway on the osteoinductive performance of Ta and Ti was assessed by up- and down-regulation of integrin α5 and β1 with RNA interference, as well as through ERK1/2 inhibition with U0126. Results: Osteogenesis of rBMSCs seeded on the Ta surface was superior to that of cells seeded on the Ti surface in terms of ALP activity, extracellular matrix calcification, and the expression of integrin α5, integrin β1, ERK1/2, Runt-related transcription factor 2, osteocalcin, collagen type I, and ALP at both the mRNA and protein levels. Moreover, down-regulation of integrin α5 or integrin β1, or ERK1/2 inhibition severely impaired the osteoblastic differentiation on the Ta surface. By contrast, over-expression of integrin α5 or integrin β1 improved osteogenesis on the Ti substrates, while subsequent ERK1/2 inhibition abrogated this effect. Conclusion: The integrin α5β1/ERK1/2 pathway plays a crucial role in regulating rBMSCs osteogenic differentiation; thus, the greater ability of a Ta surface to trigger integrin α5β1/ERK1/2 signaling may explain its better osteoinductivity. The different effects of Ta and Ti surfaces on rBMSC osteogenesis are considered to be related to the conductive behaviors between integrin α5β1 and the oxides spontaneously formed on the two metals. These results should facilitate the development of engineering strategies with Ta and Ti surfaces for improved osteogenesis in endosteal implants.
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14

Uchihara, Yoshinobu, Manabu Akahane, Takamasa Shimizu, Tomoyuki Ueha, Yusuke Morita, Shintaro Nakasaki, Tomohiko Kura, et al. "Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/629168.

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Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.
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15

Li, Yucong, Qi Pan, Nianli Zhang, Bin Wang, Zhengmeng Yang, James T. Ryaby, Erik I. Waldorff, Wayne Yuk-Wai Lee, and Gang Li. "A novel pulsed electromagnetic field promotes distraction osteogenesis via enhancing osteogenesis and angiogenesis in a rat model." Journal of Orthopaedic Translation 25 (November 2020): 87–95. http://dx.doi.org/10.1016/j.jot.2020.10.007.

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16

Li, Cairong, Jianqiao Sun, Keda Shi, Jing Long, Long Li, Yuxiao Lai, and Ling Qin. "Preparation and evaluation of osteogenic nano-MgO/PMMA bone cement for bone healing in a rat critical size calvarial defect." Journal of Materials Chemistry B 8, no. 21 (2020): 4575–86. http://dx.doi.org/10.1039/d0tb00074d.

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A series of bioactive nano-MgO/PMMA bone cements were prepared with very suitable handling and mechanical properties, good biocompatibility and osteogenic activity in vitro, excellent osteogenesis properties and bone-bonding strength in a rat critical size calvarial defect.
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17

Shen, Zhen, Zehua Chen, Xiaodong Shi, Tao Wang, Minling Huang, Guoqian Chen, Xiangling Ye, et al. "Comparison between Tonifying Kidney Yang and Yin in Treating Segmental Bone Defects Based on the Induced Membrane Technique: An Experimental Study in a Rat Model." Evidence-Based Complementary and Alternative Medicine 2020 (December 25, 2020): 1–15. http://dx.doi.org/10.1155/2020/6575127.

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Tonifying kidney therapy consisting of tonifying kidney yang and yin is the basic principle of Chinese medicine in treating segmental bone defects (SBDs). Previous studies have demonstrated the presence of the differences between tonifying kidney yang and yin in bone metabolism of osteoporosis and distraction osteogenesis models. However, whether the difference between the two tonifying kidney methods in bone repair for the induced membrane (IM) technique occurs or what is the difference remain unclear. Angiogeneic-osteogenic coupling plays an important role in bone repair and the induced membrane couples angiogenesis with the later osteogenesis during the IM process. This study aimed at investigating the effects of tonifying kidney yang (total flavonoids of Rhizoma Drynariae, TFRD) and yin (plastrum testudinis extract, PTE) on angiogenesis and osteogenesis in the IM-treated SBDs. Rats of 6 mm tibia bone defect model treated with IM were divided into five groups: the control group, the model group, the tonifying kidney yang group (TFRD-treated group), the tonifying kidney yin group (PTE-treated group), and the western medicine group. At 4 weeks after insertion of the polymethylmethacrylate (PMMA), three caudal vertebrae from the tail in each rat were implanted into the 6 mm defect gap. Radiographical, histological, immunohistochemical, and immunofluorescent analyses were performed to assess bone and vessel formation at 4 or 12 weeks after insertion of the PMMA, respectively. Our results revealed that TFRD and PTE were beneficial to both angiogenesis and osteogenesis. TFRD exerted a better effect on angiogenesis than PTE and achieved a better result in stage 1 rather than in stage 2 of IM, whereas PTE was superior to TFRD in osteogenesis and achieved a better result in stage 2 instead of stage 1. Collectively, these findings elucidated the beneficial effects of tonifying kidney yang and yin on angiogenesis and osteogenesis of SBD repair during the IM process, as well as the difference that tonifying kidney yang surpasses tonifying kidney yin in angiogenesis while tonifying kidney yin outperforms tonifying kidney yang in osteogenesis, which suggests that the combination between the application of tonifying kidney yang method in stage 1 of IM and tonifying kidney yin method in stage 2 may achieve better repair efficiency.
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18

Aronson, J., G. G. Gao, X. C. Shen, S. G. McLaren, R. A. Skinner, T. M. Badger, and C. K. Lumpkin. "The effect of aging on distraction osteogenesis in the rat." Journal of Orthopaedic Research 19, no. 3 (May 2001): 421–27. http://dx.doi.org/10.1016/s0736-0266(00)90025-1.

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19

Rowe, Norman M., Babak J. Mehrara, Matthew E. Dudziak, Douglas S. Steinbreck, Richard J. Mackool, George K. Gittes, Joseph G. McCarthy, and Michael T. Longaker. "Rat Mandibular Distraction Osteogenesis: Part I. Histologic and Radiographic Analysis." Plastic and Reconstructive Surgery 102, no. 6 (November 1998): 2022–32. http://dx.doi.org/10.1097/00006534-199811000-00033.

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20

Yasui, N., M. Sato, T. Ochi, T. Kimura, H. Kawahata, Y. Kitamura, and S. Nomura. "THREE MODES OF OSSIFICATION DURING DISTRACTION OSTEOGENESIS IN THE RAT." Journal of Bone and Joint Surgery. British volume 79-B, no. 5 (September 1997): 824–30. http://dx.doi.org/10.1302/0301-620x.79b5.0790824.

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21

Hsieh, Y. D., H. Devlin, and C. Roberts. "Early alveolar ridge osteogenesis following tooth extraction in the rat." Archives of Oral Biology 39, no. 5 (May 1994): 425–28. http://dx.doi.org/10.1016/0003-9969(94)90173-2.

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22

Chow, J. W. M., S. Fox, C. J. Jagger, and T. J. Chambers. "Role for parathyroid hormone in mechanical responsiveness of rat bone." American Journal of Physiology-Endocrinology and Metabolism 274, no. 1 (January 1, 1998): E146—E154. http://dx.doi.org/10.1152/ajpendo.1998.274.1.e146.

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We investigated the relationship between parathyroid hormone (PTH) and mechanical stimulation in mechanically induced osteogenesis. In normal rats, mechanical stimulation of the eighth caudal vertebra induced an osteogenic response. This was augmented by a single injection of human PTH-(1—34) 30–45 min before loading. No osteogenic response was seen in thyroparathyroidectomized (TPTX) rats; the osteogenic response was restored by a single injection of PTH before stimulation, suggesting that physiological levels of PTH are necessary for the mechanical responsiveness of bone. c- fosexpression was detected only in the osteocytes of those rats that were both mechanically stimulated and given PTH. This suggests that PTH supports mechanically induced osteogenesis by sensitizing either the strain-sensing mechanism itself or early responses of bone to strain-generated signals. The osteogenic response was not augmented by two further daily injections of PTH and was not seen in TPTX rats in which PTH administration was started 3 days after loading. These results reveal a major role for PTH in the mechanical responsiveness of rat bone.
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23

Miao, Yali, Yunhua Chen, Xiao Liu, Jingjing Diao, Naru Zhao, Xuetao Shi, and Yingjun Wang. "Melatonin decorated 3D-printed beta-tricalcium phosphate scaffolds promoting bone regeneration in a rat calvarial defect model." Journal of Materials Chemistry B 7, no. 20 (2019): 3250–59. http://dx.doi.org/10.1039/c8tb03361g.

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24

Shin, Sung Jin, Dong Yeon Lee, Hye Ran Lee, Jung Il Kim, Won Joon Yoo, Tae-Joon Cho, and In Ho Choi. "Enhancement of Vasculogenesis and Osteogenesis Using Granulocyte-Colony Stimulating Factor in the Rat Model of Tibial Distraction Osteogenesis." Journal of the Korean Orthopaedic Association 46, no. 5 (2011): 357. http://dx.doi.org/10.4055/jkoa.2011.46.5.357.

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25

Hasegawa, Shin, Jiro Tamura, Masashi Neo, Shunsuke Fujibayashi, Koji Goto, Yasuo Shikinami, Kenshi Okazaki, and Takashi Nakamura. "In Vivo Evaluation of Porous Hydroxyapatite/Poly D/L-lactide Composite for Bone Substitutes and Scaffolds." Key Engineering Materials 309-311 (May 2006): 1311–14. http://dx.doi.org/10.4028/www.scientific.net/kem.309-311.1311.

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We had investigated the biocompatibility, osteoconductivity, and biodegradability of a porous composite of hydroxyapatite (HA) and poly-DL-lactide (PDLLA) implanted into rabbit femoral condyles. It showed excellent osteoconductivity and biodegradability as a bone substitute. Newly formed bones were remodeled, and materials were resorbed almost completely at 78weeks after implantation. In consideration of its biocompatibility and degradability, we investigated its potential for use as a cellular scaffold and evaluated its osteoinductive property. On implantation to the rat dorsal subcutaneous tissue loaded with syngeneic bone marrow cells, osteogenesis with enchondral ossification was seen both on and in the material at 3 weeks after implantation. This osteogenesis in the HA/PDLLA tended to get mature and newly formed bone tissues were found in the material by 6weeks. To investigate the osteoinductive property material itself has, we attempted to implant this porous composite material to extra-osseous canine dorsal muscle. At 2months, osteogenesis was seen in the pores of the material. It indicated the material induced osteogenesis with intramembranous ossification process. Therefore, HA/PDLLA might be a desirable material for bone substitutes and cellar scaffolds with osteoconductive and osteoinductive property.
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Seamon, Jesse, Xiuli Wang, Fuai Cui, Tom Keller, Abhijit S. Dighe, Gary Balian, and Quanjun Cui. "Adenoviral Delivery of the VEGF and BMP-6 Genes to Rat Mesenchymal Stem Cells Potentiates Osteogenesis." Bone Marrow Research 2013 (February 26, 2013): 1–9. http://dx.doi.org/10.1155/2013/737580.

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The combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF), and bone morphogenetic protein (BMP) to sites of bone injury results in enhanced repair compared to the administration of a single factor or a combination of two factors. Based on these findings, we hypothesized that coexpression of VEGF and BMP-6 genes would enhance the osteoblastic differentiation of rat bone-marrow-derived stem cells (rMSCs) and osteogenesis by comparison to rMSCs that do not express VEGF and BMP-6. We prepared a GFP tagged adenovirus vector (Ad-VEGF+BMP-6) that contained DNA encoding the hVEGF and hBMP-6 genes. rMSCs were transduced with the virus, and the successful transduction was confirmed by green fluorescence and by production of VEGF and BMP-6 proteins. The cells were cultured to assess osteoblastic differentiation or administered in the Fischer 344 rats to assess bone formation. Mineralization of rMSCs transduced with Ad-VEGF+BMP-6 was significantly enhanced over the nontransduced rMSCs. Only transduced rMSCs could induce osteogenesis in vivo, whereas Ad-VEGF+BMP-6 or nontransduced rMSCs alone did not induce osteogenesis. The data suggests that the combined delivery of MSCs, VEGF, and BMP-6 is an attractive option for bone repair therapy.
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Panupinthu, Nattapon, Joseph T. Rogers, Lin Zhao, Luis Pastor Solano-Flores, Fred Possmayer, Stephen M. Sims, and S. Jeffrey Dixon. "P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis." Journal of Cell Biology 181, no. 5 (June 2, 2008): 859–71. http://dx.doi.org/10.1083/jcb.200708037.

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Nucleotides are released from cells in response to mechanical stimuli and signal in an autocrine/paracrine manner through cell surface P2 receptors. P2rx7−/− mice exhibit diminished appositional growth of long bones and impaired responses to mechanical loading. We find that calvarial sutures are wider in P2rx7−/− mice. Functional P2X7 receptors are expressed on osteoblasts in situ and in vitro. Activation of P2X7 receptors by exogenous nucleotides stimulates expression of osteoblast markers and enhances mineralization in cultures of rat calvarial cells. Moreover, osteogenesis is suppressed in calvarial cell cultures from P2rx7−/− mice compared with the wild type. P2X7 receptors couple to production of the potent lipid mediators lysophosphatidic acid (LPA) and prostaglandin E2. Either an LPA receptor antagonist or cyclooxygenase (COX) inhibitors abolish the stimulatory effects of P2X7 receptor activation on osteogenesis. We conclude that P2X7 receptors enhance osteoblast function through a cell-autonomous mechanism. Furthermore, a novel signaling axis links P2X7 receptors to production of LPA and COX metabolites, which in turn stimulate osteogenesis.
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28

Hamushan, Musha, Weijie Cai, Yubo Zhang, Tengfei Lou, Shaoxiang Zhang, Xiaonong Zhang, Pengfei Cheng, Changli Zhao, and Pei Han. "High-purity magnesium pin enhances bone consolidation in distraction osteogenesis model through activation of the VHL/HIF-1α/VEGF signaling." Journal of Biomaterials Applications 35, no. 2 (May 28, 2020): 224–36. http://dx.doi.org/10.1177/0885328220928550.

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Distraction osteogenesis has widespread clinical use in the treatment of large bone defects. Nonetheless, the prolonged consolidation period carries the risk of complications. Magnesium-based materials have been shown to promote bone regeneration in fracture healing both in vitro and in vivo. Here, we investigated whether high-purity magnesium could enhance bone formation in distraction osteogenesis. High-purity magnesium pins were placed into the medullary cavity in the rat distraction osteogenesis model. Results showed that the bone volume/total tissue volume, bone mineral density, and mechanical properties of new callus were significantly higher in the high-purity magnesium group compared to stainless steel and control group (p < 0.01). Histological analyses confirmed improved bone consolidation and vascularization in high-purity magnesium group. Further, polymerase chain reaction-array investigation, Western blot, and immunohistochemical results found that vascular endothelial growth factor and hypoxia inducible factor-1α were highly expressed in the high-purity magnesium group, while Von Hippel–Lindau protein was the opposite (p < 0.01). In conclusion, high-purity magnesium implants have the potential to enhance angiogenesis and bone consolidation in the distraction osteogenesis application, and this process might be via the regulation of Von Hippel–Lindau/hypoxia inducible factor-1α/vascular endothelial growth factor signaling.
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29

Wu, T., J. Zhang, B. Wang, Y. Sun, Y. Liu, and G. Li. "Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing." Bone & Joint Research 7, no. 2 (February 2018): 179–86. http://dx.doi.org/10.1302/2046-3758.72.bjr-2017-0229.r1.

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Objectives As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint Res 2018;7:179–186. DOI: 10.1302/2046-3758.72.BJR-2017-0229.R1.
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30

Chida, Norifumi, Hiroko Takita, Yoshio Imai, Toshitake Obata, Satoru Yamamoto, Tadashi Iizuka, Masanobu Shindoh, Takao Kohgo, and Atsuro Yokoyama. "Osteogenesis Around Dental Implants Combined with Cultured Rat Bone Marrow Cells." Oral Medicine & Pathology 11, no. 4 (2006): 89–96. http://dx.doi.org/10.3353/omp.11.89.

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31

Fukunaga, Tsutana, Shogo Masumi, Hirokazu Yano, Shuji Ikebe, and Kei Shimizu. "Osteogenesis in xenogeneic bone transplantation, using an immunosuppressant: Rabbit-rat experiments." Acta Orthopaedica Scandinavica 66, no. 6 (January 1995): 557–60. http://dx.doi.org/10.3109/17453679509002315.

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32

Nowazesh Ali, Mir, Sadakazu Ejiri, Tadaharu Kobayashi, Rezwana Binte Anwar, Kimimitsu Oda, Hayato Ohshima, and Chikara Saito. "Histologic study of the cellular events during rat mandibular distraction osteogenesis." Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 107, no. 3 (March 2009): 325–35. http://dx.doi.org/10.1016/j.tripleo.2008.06.030.

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33

Aronson, J., W. R. Hogue, C. M. Flahiff, G. G. Gao, X. C. Shen, R. A. Skinner, T. M. Badger, and C. K. Lumpkin. "Development of tensile strength during distraction osteogenesis in a rat model." Journal of Orthopaedic Research 19, no. 1 (January 2001): 64–69. http://dx.doi.org/10.1016/s0736-0266(00)00002-4.

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34

Li, Xudong, Ge Feng, Songsong Zhu, Jihua Li, En Luo, and Jing Hu. "Osteogenesis response to implanted materials in endocortical bone in rat femora." Journal of Orthopaedic Science 17, no. 5 (September 2012): 626–33. http://dx.doi.org/10.1007/s00776-012-0254-4.

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35

Deshpande, Sagar S., Laura A. Monson, Christi M. Cavaliere, Alexander L. Ayzengart, and Steven R. Buchman. "Distraction Osteogenesis Following Low-Dose Hyperfractionated Irradiation in the Rat Mandible." Journal of Oral and Maxillofacial Surgery 71, no. 8 (August 2013): 1465–70. http://dx.doi.org/10.1016/j.joms.2013.02.011.

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36

Kawakami, Sawako, Makoto Shiota, Kazuhiro Kon, Wataru Kozuma, Hajime Iijima, and Shohei Kasugai. "Application of dissociated soft tissue using rat palatal mucosa on osteogenesis." Clinical Oral Implants Research 29 (October 2018): 159. http://dx.doi.org/10.1111/clr.44_13358.

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37

Perrien, Daniel S., Elizabeth C. Brown, James Aronson, Robert A. Skinner, Donna C. Montague, Thomas M. Badger, and Charles K. Lumpkin. "Immunohistochemical Study of Osteopontin Expression During Distraction Osteogenesis in the Rat." Journal of Histochemistry & Cytochemistry 50, no. 4 (April 2002): 567–74. http://dx.doi.org/10.1177/002215540205000414.

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38

Warren, Stephen M., Babak J. Mehrara, Douglas S. Steinbrech, Michael F. Paccione, Joshua A. Greenwald, Jason A. Spector, and Michael T. Longaker. "Rat Mandibular Distraction Osteogenesis: Part III. Gradual Distraction versus Acute Lengthening." Plastic and Reconstructive Surgery 107, no. 2 (February 2001): 441–53. http://dx.doi.org/10.1097/00006534-200102000-00021.

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39

Loboa, Elizabeth G., Tony D. Fang, Stephen M. Warren, Derek P. Lindsey, Kenton D. Fong, Michael T. Longaker, and Dennis R. Carter. "Mechanobiology of mandibular distraction osteogenesis: experimental analyses with a rat model." Bone 34, no. 2 (February 2004): 336–43. http://dx.doi.org/10.1016/j.bone.2003.10.012.

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40

Pujadas Bigi, M. M., S. Kokubu, M. Lewicki, M. M. Nenda, A. M. Ubios, and P. M. Mandalunis. "An experimental model of distraction osteogenesis in rat mandibular alveolar bone." Bone 48, no. 6 (June 2011): S287. http://dx.doi.org/10.1016/j.bone.2011.03.735.

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41

Zhang, Mingyu, Kunzheng Wang, Zhibin Shi, Huaqing Yang, Xiaoqian Dang, and Wei Wang. "Osteogenesis of the construct combined BMSCs with β-TCP in rat." Journal of Plastic, Reconstructive & Aesthetic Surgery 63, no. 2 (February 2010): 227–32. http://dx.doi.org/10.1016/j.bjps.2008.11.017.

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42

Tanaka, Shigeo M., Yuma Yorozuya, and Daisuke Takatsu. "Random Electromyostimulation Promotes Osteogenesis and the Mechanical Properties of Rat Bones." Annals of Biomedical Engineering 45, no. 12 (September 19, 2017): 2837–46. http://dx.doi.org/10.1007/s10439-017-1927-0.

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43

Bluhm, Andrew E., and Daniel M. Laskin. "The effect of polytetrafluoroethylene cylinders on osteogenesis in rat fibular defects." Journal of Oral and Maxillofacial Surgery 53, no. 2 (February 1995): 163–66. http://dx.doi.org/10.1016/0278-2391(95)90395-x.

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44

Bae, Chun-Sik, Seung-Hyun Kim, Taeho Ahn, Yeonji Kim, Se-Eun Kim, Seong-Soo Kang, Jae-Sung Kwon, Kwang-Mahn Kim, Sahng-Gyoon Kim, and Daniel Oh. "Multiple Porous Synthetic Bone Graft Comprising Engineered Micro-Channel for Drug Carrier and Bone Regeneration." Materials 14, no. 18 (September 15, 2021): 5320. http://dx.doi.org/10.3390/ma14185320.

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Due to high demand but limited supply, there has been an increase in the need to replace autologous bone grafts with alternatives that fulfill osteogenic requirements. In this study, two different types of bone grafts were tested for their drug carrying abilities along with their osteogenic properties. Two different types of alendronate-loaded bone grafts, Bio-Oss (bovine bone graft) and InRoad (biphasic synthetic bone graft) were observed to see how different concentrations of alendronate would affect the sustained release to enhance osteogenesis. In this study, defected ovariectomize-induced osteoporotic rat calvarias were observed for 28 days with three different concentrations of alendronate (0 mg, 1 mg, 5 mg) for both Bio-Oss and InRoad. A higher concentration (5 mg) allowed for a more controlled and sustained release throughout the 28-day comparison to those of lower concentrations (0 mg, 1 mg). When comparing Bio-Oss and InRoad through histology and Micro-CT, InRoad showed higher enhancement in osteogenesis. Through this study, it was observed that alendronate not only brings out robust osteogenesis with InRoad bone grafts, but also enhances bone regeneration in an alendronate-concentration-dependent manner. The combination of higher concentration of alendronate and multiple porous bone graft containing internal micro-channel structure of InRoad resulted in higher osteogenesis with a sustained release of alendronate.
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45

Kanjilal, Deboleena, Christopher Grieg, Maya Deza Culbertson, Sheldon S. Lin, Michael Vives, Joseph Benevenia, and J. Patrick O’Connor. "Improved osteogenesis in rat femur segmental defects treated with human allograft and zinc adjuvants." Experimental Biology and Medicine 246, no. 16 (May 26, 2021): 1857–68. http://dx.doi.org/10.1177/15353702211019008.

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Bone allograft is widely used to treat large bone defects or complex fractures. However, processing methods can significantly compromise allograft osteogenic activity. Adjuvants that can restore the osteogenic activity of processed allograft should improve clinical outcomes. In this study, zinc was tested as an adjuvant to increase the osteogenic activity of human allograft in a Rag2 null rat femoral defect model. Femoral defects were treated with human demineralized bone matrix (DBM) mixed with carboxy methyl cellulose containing ZnCl2 (0, 75, 150, 300 µg) or Zn stearate (347 µg). Rat femur defects treated with DBM-ZnCl2 (75 µg) and DBM-Zn stearate (347 µg) showed increased calcified tissue in the defect site compared to DBM alone. Radiograph scoring and µCT (microcomputed tomography) analysis showed an increased amount of bone formation at the defects treated with DBM-Zn stearate. Use of zinc as an adjuvant was also tested using human cancellous bone chips. The bone chips were soaked in ZnCl2 solutions before being added to defect sites. Zn adsorbed onto the chips in a time- and concentration-dependent manner. Rat femur defects treated with Zn-bound bone chips had more new bone in the defects based on µCT and histomorphometric analyses. The results indicate that zinc supplementation of human bone allograft improves allograft osteogenic activity in the rat femur defect model.
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46

Hu, Hongyang, Min Chen, Guangzu Dai, Guoqing Du, Xuezong Wang, Jie He, Yongfang Zhao, et al. "An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways." Cellular Physiology and Biochemistry 38, no. 6 (2016): 2375–88. http://dx.doi.org/10.1159/000445590.

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Background/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 µM, 12.5 µM, and 25 µM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/β-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/β-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/β-catenin and Erk1/2-MAPK signaling pathways.
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47

Singh, SU, RF Casper, PC Fritz, B. Sukhu, B. Ganss, B. Girard, JF Savouret, and HC Tenenbaum. "Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol." Journal of Endocrinology 167, no. 1 (October 1, 2000): 183–95. http://dx.doi.org/10.1677/joe.0.1670183.

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Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smoke-associated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4'-trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0.01 vs control) in the presence of 10(-9) M TCDD and these effects were reversed by 10(-6) M resveratrol (P<0.05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10(-10)M) caused an approximately 33% reduction in AP activity, which was abrogated by 3. 5x10(-7) M resveratrol. TCDD also induced a marked reduction in mineralization ( approximately 75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss.
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48

Lei, Lei, Zhongning Liu, Pingyun Yuan, Ronghua Jin, Xiangdong Wang, Ting Jiang, and Xin Chen. "Injectable colloidal hydrogel with mesoporous silica nanoparticles for sustained co-release of microRNA-222 and aspirin to achieve innervated bone regeneration in rat mandibular defects." Journal of Materials Chemistry B 7, no. 16 (2019): 2722–35. http://dx.doi.org/10.1039/c9tb00025a.

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49

Shurygina, E. I., V. S. Polyakova, and V. A. Mikhanov. "Morphological Changes in Thyroid and Parathyroid Glands During the Reparative Osteogenesis." Journal of Anatomy and Histopathology 7, no. 2 (July 3, 2018): 90–94. http://dx.doi.org/10.18499/2225-7357-2018-7-2-90-94.

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The aim of the research is to study the dynamics of structural and functional changes in the thyroid and parathyroid glands during reparative osteogenesis. Material and methods. The study was performed on 40 adult males rat of the Wistar line, weighing 180.0±10.0 g. A model of an open fracture of the tibial diaphysis was used in the experimental group. The control group was intact. Structural changes in bone callus, thyroid and parathyroid glands were studied using immunohistochemistry methods, light microscopy, morphometry and statistics. Results. The proliferative and functional activity of the major endocrinocytes of the parathyroid glands is increased in the initial periods of reparative osteogenesis, resulting in an increasing of osteoclastic activity with resorption of bone fragments in the fracture zone. From 21th day of osteogenesis the functional activity of the parathyroid glands is reduced, the activity of the C-cells of the thyroid gland is activated; then the functional activity of C-cells is decreased. Conclusion. The observed changes in the synthetic and proliferative activity of C-cells and parathyrocytes have a certain time interval, which correlates with the histogenesis of bone tissue in the fracture zone.
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50

Hwang, Il Ung, Tae Joon Cho, In Ho Choi, Chin Youb Chung, Won Joon Yoo, and Eun Hee Kim. "Expression of Pro-inflammatory Cytokines during Distraction Osteogenesis of the Rat Tibia." Journal of the Korean Orthopaedic Association 39, no. 1 (2004): 81. http://dx.doi.org/10.4055/jkoa.2004.39.1.81.

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