We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2.

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Articular cartilage has a limited capacity for spontaneous repair, and an effective method to repair damaged articular cartilage has not yet been established. The purpose of this study was to evaluate the effect of transplantation of porous hydroxyapatite collagen (HAp/Col) impregnated with bone morphogenetic protein‐2 (BMP‐2). To evaluate the characteristics of porous HAp/Col as a drug delivery carrier of recombinant human BMP‐2 (rhBMP‐2), the rhBMP‐2 adsorption capacity and release kinetics of porous HAp/Col were analyzed. Porous HAp/Col impregnated with different amounts of rhBMP‐2 (0, 5, and 25 μg) was implanted into osteochondral defects generated in the patellar groove of Japanese white rabbits to evaluate the effect on osteochondral defect regeneration. At 3, 6, 12, and 24 weeks after operation, samples were harvested and subjected to micro‐computed tomography analysis and histological evaluation of articular cartilage and subchondral bone repair. The adsorption capacity was 329.4 μg of rhBMP‐2 per cm3 of porous HAp/Col. Although 36% of rhBMP‐2 was released within 24 h, more than 50% of the rhBMP‐2 was retained in the porous HAp/Col through the course of the experiment. Defects treated with 5 μg of rhBMP‐2 showed the most extensive subchondral bone repair and the highest histological regeneration score, and differences against the untreated defect group were significant. The histological regeneration score of defects treated with 25 μg of rhBMP‐2 increased up to 6 weeks after implantation, but then decreased. Porous HAp/Col, therefore, is an appropriate carrier for rhBMP‐2. Implantation of porous HAp/Col impregnated with rhBMP‐2 is effective for rigid subchondral bone repair, which is important for the repair of the smooth articular surface.

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The potential teratogenic effects and fetal toxicity of environmental estrogenic endocrine disruptors have become a great concern in recent years, and they have yet to be fully characterized. In the present study, the teratogenic effects of bisphenol A (BPA) and genistein (GEN) on rat embryos during their critical period of organogenesis were investigated using a whole-embryo culture experiment. The combined exposure effects of BPA and GEN were explored using a 4 x 4 full factorial design. Both BPA and GEN produced concentration-dependent inhibition of embryonic development, beginning at 32.0 and 10.0 microg/ml, respectively. Full factorial and isobologram analyses revealed a significant synergistic interaction between BPA and GEN for most end points (12 out of 20 tested), as indicated by the enhanced developmental toxicity of BPA after coexposure with different dose levels of GEN. In particular, serious malformations and a higher abnormal frequency of the central nervous system were induced by the combination of BPA and GEN. Our findings suggest that GEN may be embryotoxic and teratogenic to humans. BPA alone may not be a potential teratogen, but these two estrogenic chemicals have a synergistic effect on embryonic development when present together during the critical period of major organ formation. The current findings suggest that pregnant women should not take soy supplements, but more studies are necessary to provide a conclusive recommendation.

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In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018.