Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis

• Published in: Pharmaceutical biology 2024-12, Vol.62 (1), p.42-52
• Main Authors: Liang, Bing, Chen, Xiongbin, Li, Min, Zhang, Lingling, Yang, Xia, Shi, Liangqin, Gong, Yanju, Gong, Yuanyuan, Xu, Huan, Wu, Xiao, Jin, Zhong, Wang, Yanru, Liu, Luwei, Yi, Xiaohong, Xie, Lushuang, Zhong, Hua, Shen, Chongyang, Wang, Yong, Yang, Lan
• Format: Article
• Language: English
• Subjects: Adipogenesis; Animals; Autophagy; Autophagy-Related Proteins - metabolism; Autophagy-Related Proteins - pharmacology; Bone loss; Bone marrow; Cell cycle; Cell Differentiation; Cell viability; Female; Gene expression; GTP-binding protein; Humans; Lipogenesis; Mesenchymal Stem Cells; mRNA; Oophorectomy; Osteogenesis; Osteoporosis; Ovariectomy; p53 Protein; Post-menopause; postmenopausal osteoporosis (P MOP); Proteins; Rats; Rats, Sprague-Dawley; Senescence; Traditional Chinese medicine; Western blotting; YAP-Signaling Proteins; Yes-associated protein
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2023.2291675

Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). To explore the effects and mechanisms of action of LWDH in PMOP. Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.