First Author | Xia C | Year | 2020 |
Journal | Biomed Pharmacother | Volume | 127 |
Pages | 110170 | PubMed ID | 32334373 |
Mgi Jnum | J:314480 | Mgi Id | MGI:6819701 |
Doi | 10.1016/j.biopha.2020.110170 | Citation | Xia C, et al. (2020) Bushenhuoxue formula promotes osteogenic differentiation of growth plate chondrocytes through beta-catenin-dependent manner during osteoporosis. Biomed Pharmacother 127:110170 |
abstractText | BACKGROUND: Bushenhuoxue formula (BSHXF) has shown excellent clinical effects on the treatment of osteoporosis in China. The aim of this study is to determine the anti-osteoporosis effects and precise molecular mechanisms of BSHXF on mouse models. METHODS: Ten-week-old female C57BL/6 J mice were subjected to ovariectomy and provided a daily treatment of BSHXF. At 8 weeks post-surgery, the femurs were harvested for tissue analyses including muCT, histology, qRT-PCR and immunohistochemical (IHC) staining of beta-catenin, ALP and FABP4. To investigate the role of beta-catenin in the anti-osteoporosis effects of BSHXF, relative experiments mentioned above were performed in beta-catenin conditional knockout mice. RESULTS: Ovariectomized (OVX) mice presented severe bone loss and excessive fat accumulation in the chondro-osseous junction underneath the growth plate, with decreased expression of ALP and increased expression of FABP4. BSHXF significantly recovered the OVX-induced abnormal osteogenesis and adipogenesis with the activation of beta-catenin in growth plate chondrocytes. Further, we generated growth plate chondrocyte-specific beta-catenin knockout (beta-catenin(Gli1ER)) mice that exhibited bone loss and fat accumulation in the chondro-osseous junction, similar to the OVX mice. However, BSHXF failed to rescue the osteoporosis-like phenotype in beta-catenin(Gli1ER) mice, indicating the anti-osteoporosis effects of BSHXF act mainly through beta-catenin signaling. No significant restoration of ALP and FABP4 was observed in beta-catenin(Gli1ER) mice after the treatment of BSHXF. CONCLUSIONS: BSHXF attenuates osteoporosis by promoting osteogenic differentiation of growth plate chondrocytes mainly in beta-catenin-dependent manner. BSHXF is considered as a new candidate for the treatment of osteoporosis. |