Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Bushen Huoxue Decoction alleviates osteoporosis by promoting the osteogenic differentiation of BMSCs by targeting the OTUD5/PDCD5/p53 signaling pathway.
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Chen Xin, Han Huawei, Tian Ningsheng, Jin Jie, Sun Yang, Guo Ziwen, Zhou Min, Wang Jiahui, Liao Taiyang, Xu Ziqing, Teng Jiasong, Song Yuchen, Wu Lan, Li Zhiwei
Аннотация
BACKGROUND: A decline in the osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMSCs) constitutes a central event in the disruption of bone homeostasis in osteoporosis (OP). Bushen Huoxue Decoction (BSHXD), a traditional Chinese medicinal formula, has demonstrated clinical efficacy; however, its specific therapeutic effects and underlying mechanisms in the treatment of OP remain to be fully elucidated.
PURPOSE: This work aimed to elucidate the mechanisms by which BSHXD mitigates OP and to explore its therapeutic potential.
METHODS: First, the bioactive constituents of BSHXD were identified using LC-MS/MS analysis. In vivo, the effects of BSHXD on bone mineral density and microarchitecture were evaluated in an ovariectomized (OVX) mouse model through micro-CT, H&E staining, and IHC analysis. In vitro, the pro-osteogenic effects of BSHXD on the differentiation of BMSCs into osteoblasts were assessed using ALP staining, Alizarin Red S staining, Western blotting, and RT-qPCR. Furthermore, to elucidate the underlying mechanisms by which BSHXD regulates osteogenic differentiation of BMSCs, proteomic sequencing, protein co-expression network analysis, network pharmacology, Co-IP, and lentiviral-mediated overexpression assays were performed.
RESULTS: In vivo experiments demonstrated that medium- and high-dose BSHXD significantly increased bone mineral density in OVX mice, enhanced bone formation, and attenuated OVX-induced bone loss. In vitro, BSHXD treatment markedly promoted the osteogenic differentiation capacity of BMSCs. Proteomic analysis coupled with protein co-expression network analysis indicated that OTUD5 may represent a key therapeutic target in OP. Mechanistically, at the protein level, BSHXD downregulated OTUD5 expression and facilitated the ubiquitin-dependent degradation of PDCD5, thereby suppressing p53 activation and upregulating osteogenesis-related genes, ultimately enhancing the osteogenic differentiation of BMSCs. Notably, OTUD5 overexpression abrogated the therapeutic effects of BSHXD.
CONCLUSION: Collectively, BSHXD exerts a promoting action on BMSCs osteogenic differentiation via the OTUD5/PDCD5/p53 signaling pathway, thereby alleviating osteoporotic bone metabolic imbalance. These observations highlight the therapeutic potential of targeting BMSCs for OP treatment and provide mechanistic evidence supporting the use of BSHXD in the prevention and management of OP.
PURPOSE: This work aimed to elucidate the mechanisms by which BSHXD mitigates OP and to explore its therapeutic potential.
METHODS: First, the bioactive constituents of BSHXD were identified using LC-MS/MS analysis. In vivo, the effects of BSHXD on bone mineral density and microarchitecture were evaluated in an ovariectomized (OVX) mouse model through micro-CT, H&E staining, and IHC analysis. In vitro, the pro-osteogenic effects of BSHXD on the differentiation of BMSCs into osteoblasts were assessed using ALP staining, Alizarin Red S staining, Western blotting, and RT-qPCR. Furthermore, to elucidate the underlying mechanisms by which BSHXD regulates osteogenic differentiation of BMSCs, proteomic sequencing, protein co-expression network analysis, network pharmacology, Co-IP, and lentiviral-mediated overexpression assays were performed.
RESULTS: In vivo experiments demonstrated that medium- and high-dose BSHXD significantly increased bone mineral density in OVX mice, enhanced bone formation, and attenuated OVX-induced bone loss. In vitro, BSHXD treatment markedly promoted the osteogenic differentiation capacity of BMSCs. Proteomic analysis coupled with protein co-expression network analysis indicated that OTUD5 may represent a key therapeutic target in OP. Mechanistically, at the protein level, BSHXD downregulated OTUD5 expression and facilitated the ubiquitin-dependent degradation of PDCD5, thereby suppressing p53 activation and upregulating osteogenesis-related genes, ultimately enhancing the osteogenic differentiation of BMSCs. Notably, OTUD5 overexpression abrogated the therapeutic effects of BSHXD.
CONCLUSION: Collectively, BSHXD exerts a promoting action on BMSCs osteogenic differentiation via the OTUD5/PDCD5/p53 signaling pathway, thereby alleviating osteoporotic bone metabolic imbalance. These observations highlight the therapeutic potential of targeting BMSCs for OP treatment and provide mechanistic evidence supporting the use of BSHXD in the prevention and management of OP.