Bushenhuoxue formula promotes osteogenic differentiation of growth plate chondrocytes through β-catenin-dependent manner during osteoporosis

Autor: Chenjie Xia, Zhen Zou, Liang Fang, Qinwen Ge, Peng Zhang, Huihui Xu, Rui Xu, Zhenyu Shi, Houfu Lin, Xinyi Ding, Luwei Xiao, Peijian Tong, Ping-er Wang, Hongting Jin
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Biomedicine & Pharmacotherapy, Vol 127, Iss , Pp 110170- (2020)
Druh dokumentu: article
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2020.110170
Popis: 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 μCT, histology, qRT-PCR and immunohistochemical (IHC) staining of β-catenin, ALP and FABP4. To investigate the role of β-catenin in the anti-osteoporosis effects of BSHXF, relative experiments mentioned above were performed in β-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 β-catenin in growth plate chondrocytes. Further, we generated growth plate chondrocyte-specific β-catenin knockout (β-cateninGli1ER) 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 β-cateninGli1ER mice, indicating the anti-osteoporosis effects of BSHXF act mainly through β-catenin signaling. No significant restoration of ALP and FABP4 was observed in β-cateninGli1ER mice after the treatment of BSHXF. Conclusions: BSHXF attenuates osteoporosis by promoting osteogenic differentiation of growth plate chondrocytes mainly in β-catenin-dependent manner. BSHXF is considered as a new candidate for the treatment of osteoporosis.
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