鸢尾素调节Hippo/YAP信号通路对绝经后骨质疏松大鼠骨代谢的调节作用

doi:10.3969/j.issn.1006-6233.2024.02.017

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Abstract Objective: To investigate the effects of irisin on bone metabolism and Hippo/Yes associated protein (YAP) signaling pathway in postmenopausal osteoporosis (PMOP) rats. Methods: A PMOP rat model was established using bilateral ovariectomy. All experimental rats divided into the following groups: control group, PMOP group, irisin low, medium, and high dose groups (Irisin-L, Irisin-M, Irisin-H groups), and high-dose irisin+YAP inhibitor Vitipofen group (Irisin-H+VTPF group); bone mineral density meter was applied to measure bone mineral density (BMD); Micro-CT was applied to analyze the average thickness of trabeculae (Tb.Th), percentage of trabecular area (Tb.Ar), number of trabeculae (Tb.N), and trabecular separation (Tb.SP); HE staining was applied to observe the morphological changes of femoral tissue; ELISA method was applied to detect the levels of bone metabolism biomarkers specific alkaline phosphatase (BALP), procollagen type Ⅰ N-terminal propeptide (PINP), osteocalcin (OC), and core binding factor-α1 (CBF-α1) in serum; Western blot method was applied to detect the expression levels of transcriptional co-activator with PDZ-binding motif (TAZ), YAP, and p-YAP proteins. Results: Compared with the Control group, the trabecular bone structure of the femoral bone tissue in the PMOP group was disordered, the trabecular bone thickness was decreased, the bone marrow space was significantly increased, and even mild fractures occurred. The levels of BMD, Tb.Th, Tb.Ar, Tb.N, BALP, PINP, OC, RANKL, TAZ, YAP, and p-YAP were significantly decreased, and Tb.Sp was significantly increased (P < 0.05). Compared with the PMOP group, the trabecular bone structure of the femoral bone tissue in the Irisin-L, Irisin-M, and Irisin-H groups was gradually arranged in order, the bone marrow space was reduced, and the femoral bone tissue damage was gradually alleviated. The levels of BMD, Tb.Th, Tb.Ar, Tb.N, BALP, PINP, OC, RANKL, TAZ, YAP, and p-YAP were significantly increased in order, and Tb.Sp was significantly decreased in order (P < 0.05). Compared with the Irisin-H group, the trabecular bone structure of the femoral bone tissue in the Irisin-H + VTPF group was disordered, the bone marrow space was significantly increased, the femoral bone tissue damage was aggravated, and the levels of BMD, Tb.Th, Tb.Ar, Tb.N, BALP, PINP, OC, RANKL, TAZ, YAP, and p-YAP were significantly decreased, and Tb.Sp was significantly increased (P < 0.05). Conclusion: Irisin can prevent and treat osteoporosis by regulating bone metabolism in OVX osteoporotic rats through the activation of the Hippo/YAP signaling pathway.

Key words： Irisin Hippo-YAP signaling pathway Postmenopausal osteoporosis Bone metabolism

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.02.017 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I2/264

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