基于Hippo-YAP/TAZ通路分析白果内酯抑制OA大鼠软骨退变的作用机制

doi:10.11843/j.issn.0366-6964.2025.12.043

Abstract

Abstract: The aim of this study was to reveal and validate the improvement effect of bilobalide (BB) on cartilage degeneration in a rat osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT) via the Hippo-YAP/TAZ pathway. Forty-five male Sprague-Dawley (SD) rats were randomly divided into the control group, model group (OA group) and drug intervention group (BB group). In addition to the control group, the rat OA model was constructed by ACLT method. The rats in the BB group were given 10 mg·kg^-1 BB daily for 6 weeks, after that, knee joint and cartilage tissue samples were taken for consequtive examination. After the operation, the rats in each group were examined once a week for joint swelling. The degree of cartilage degeneration of rats was evaluated by gross observation, Pelletier score, histological observation and the OARSI score. The degree of subchondral bone injury was observed by Micro-CT, and the levels of Hippo-YAP/TAZ pathway related proteins MST1, LATS1, YAP and TAZ, as well as the cartilage extracellular matrix (ECM) degradation protein MMP-3 were detected by Western blot.Computer molecular docking was used to predict the binding affinity of BB to potential targets. The results showed that in an ACLT-induced OA model, BB could inhibit joint swelling, alleviate cartilage pathological features and highly significantly reduce OARSI score (P<0.01). It also mitigated damage to the subchondral trabecular structure and ameliorated OA-related cartilage degeneration. In terms of mechanism, BB highly significantly increased the levels of MST1 and LATS1 in Hippo-YAP/TAZ pathway in rat cartilage (P<0.01), inhibited the expression of YAP and TAZ in the nucleus (P<0.01), and decreased the expression of MMP-3 (P<0.01), thus playing an anti-ECM degradation role. In addition, molecular docking showed that BB had good affinity with YAP and TAZ (binding energy<-20.92 kJ·mol^-1). The results suggested that BB inhibited the degradation of cartilage ECM, alleviated joint swelling and inhibited cartilage degeneration through Hippo-YAP/TAZ pathway, and played a role in improving OA.

Key words: osteoarthritis, cartilage degeneration, bilobalide, Hippo-YAP/TAZ pathway, natural product

CLC Number:

S857.16+15

QIU Zongsheng, LI Shuxin, QI Jingjing, GUO Xiaoyan, MA Yuhui, ZHANG Zhiheng, WANG Ruilong, WANG Haiyang, LI Yanan, MA Tianwen. Analysis of the Mechanism of Bilobalide in Inhibiting Cartilage Degeneration in OA Rats based on Hippo-YAP/TAZ Pathway[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(12): 6422-6430.

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Analysis of the Mechanism of Bilobalide in Inhibiting Cartilage Degeneration in OA Rats based on Hippo-YAP/TAZ Pathway

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