Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/β-catenin pathways
Tianwen Ma, Hongri Ruan, Liangyu Lv, Chengwei Wei, Yue Yu, Lina Jia, Xiaopeng Song, Jiantao Zhang, Yanan Li
Abstract
experiments. We found that OLA promoted interleukin-1β (IL-1β)-induced production of type II collagen (collagen II) in rat chondrocytes, decreased the expression of matrix metalloproteinase (MMP)-3 and MMP-13, and inhibited inflammatory cytokine (IL-1β and TNF-α) and cartilage marker (CTX-II and COMP) levels, thereby hindering the pathological process of cartilage. Mechanistically, OLA inhibited the Wnt/β-catenin pathway, activated the Hippo/YAP pathway, and hampered the ECM degradation process by inhibiting the nuclear translocation of β-catenin and YAP. When we knocked down β-catenin, OLA lost its stimulatory effect on the Hippo pathway. These findings confirm that OLA plays an anti-ECM degradation role by regulating the Wnt/β-catenin and Hippo/YAP pathways. Overall, this study provides a theoretical basis for developing highly effective and low-toxic natural products for the prevention and treatment of OA.