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Selective inhibitors of the osteoblast proteasome have been demonstrated to significantly enhance bone formation in vitro and in vivo. Specific proteasome inhibitors, such as epoxomicin and proteasome inhibitor-1, have been shown to increase bone volume and formation rates by over 70% in mice, correlating with elevated mRNA expression of BMP-2. Mechanistic studies indicate that these inhibitors regulate BMP-2 gene expression through the inhibition of Gli3 proteolytic processing, suggesting potential therapeutic applications in managing bone loss diseases.
Journal of Clinical Investigation, 2003
Developmental biology, 1987
Journal of Biomedical Materials Research Part A, 2008
Bone morphogenetic proteins (BMPs) are factors that promote osteoblastic differentiation and osteogenesis. The aim of this study was to examine the behavior of neonatal rat calvarial osteoblast cells cultured on different concentrations of BMP graft materials. Fifty thousand cells per milliliter were seeded and cultured on graft materials for 24 and 48 h. Different concentrations of BMPs (combination of BMPs numbered from 1 to 14) were supplemented to the medium. To evaluate cellular proliferation and differentiation, specimens were examined for DNA synthesis, alkaline phosphatase (ALP) activity, cell numbers, and viability of the cells. Further, transforming growth factor-b 1 (TGF-b 1 ) and lactate dehydrogenase (LDH) levels were investigated. Morphological appearance of the specimens at 24 and 48 h of incubation was evaluated using scanning electron microcopy. Evaluations of DNA synthesis, cell count, and cell viability data revealed that a significant difference existed at 24 and 48 h (p < 0.05). The TGF-b 1 and ALP analysis showed only a significant difference between the groups at the end of 24 h (p < 0.05). Regarding the lactate dehydrogenase activity there was not any significant difference at 24 and 48 h (p > 0.05). No morphological differences were observed in cell morphology on BMP graft material and the control group. These results indicate that BMPs have an inductive effect on osteoblast differentiation and a possible inhibitory effect in the early phases of cell proliferation.
Journal of Oral and Maxillofacial Surgery, 1992
Bone matrix-derived bone morphogenetic protein (BMP) was extracted from bovine, porcine, rabbit, Sprague-Dawley rat, and Wistar rat bone and purified. The purified fractions all had similar molecular weights and induced new bone in 3 weeks when implanted into muscle pouches of Wistar rats. Bone matrix-derived BMP is believed to consist of subunits and that of different animal origin to contain the same fraction with BMP activity. Bone morphogenetic protein (BMP) exists in the bone matrix and acts on immature mesenchymal cells to initiate bone induction through endochondral bone differemiation.l? Other factors that have been reported to be present in the bone matrix and haveB-MP-like activity include osteoinductive factor (OIF),6 osteogenin,? and cartilage-inducing factor (CIF).8 Of three BMP types reported by Wozney et al,9 two (BMP-2A, BMP-3) were new members of the TGF-fj family. In our previous study, 10 we compared BMP derived from the rabbit bone, dentin, and wound tissue. These proteins had similar activities, but were different in many other respects, and their identification has not been clarified. Many investigators have reported excellent methods for the isolation and purification ofBMP. I 1,12 However, a method for the synthesis of BMP in large quantities and for the purification of BMP derived from various animals and tissues remains to be developed. In this study, we extracted and purified BMP from bovine, porcine, rabbit, Sprague-Dawley rat, and Wistar rat
Journal of Biomedical Materials Research Part A, 2011
The aim of this study was to observe the osteogenic activity of native bone morphogenetic proteins (BMPs) obtained from different species including bovine, ostrich and emu sources in order to compare mammalian and avian BMPs. Rat mesenchymal progenitor marrow stromal cells and pre-osteoblastic C2C12 cell cultures, were exposed to the native BMPs and alkaline phosphatase (ALP) and creatine kinase (CK) levels were determined by assay. The results showed that the ALP activity in C2C12 cultures was elevated by bovine BMP by 2-to 10-fold (p < 0.05-0.001) from day 3 during 14 days. There were no significant differences in avian BMP related elevations of ALP activity except with ostrich BMPs at day 14 (p < 0.05). However, exposure of MSCs cultures to BMPs derived from bovine, ostrich or emu sources resulted in elevated ALP from day 3 (p < 0.05). Bovine BMP resulted in more ALP elevation than with either of the avian BMPs. All of BMPs elevated Creatine kinase (CK) activity from day 1 and climbed until peaking at day 7. Compared with control cultures, CK was elevated more with exposure to emu BMP and was more elevated with greater statistical significance than with bovine and ostrich BMP before day 5. These higher levels remained until day 14 (p < 0.05). The results of this study suggest that both bovine and avian BMPs are able to stimulate osteogenesis in mature osteoblasts in vitro. The strongest synergistic effect on osteogenesis was detected in cells stimulated with bovine BMP. Avian BMPs had lower effects on ALP and CK activity, emu BMP being more effective than ostrich BMP. V C 2011
Endocrinology, 1995
Materialwissenschaft und Werkstofftechnik, 2001
British Journal of Haematology, 2007
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