GA-017 attenuates OA by activating YAP/TAZ

Osteoarthritis (OA) is a common disease that causes joint pain, mobility issues, and functional impairment in middle-aged and older individuals. However, effective medications for its treatment are lacking. YAP (Yes-associated protein) /TAZ (transcriptional co-activator with PDZ-binding motif) are important protective molecules that regulate the development of OA, and activating YAP/TAZ may be a potential treatment strategy. GA-017 is an inhibitor of LATS (large tumor suppressor kinase), an upstream molecule of YAP/TAZ in the Hippo signaling pathway, and has the potential to activate YAP/TAZ. However, whether GA-017 regulates chondrocyte metabolism and arthritis progression through YAP/TAZ activation remains unclear. In this study, we found that GA-017 activated YAP/TAZ and inhibited NF-κB (nuclear factor kappaB) signaling, thereby regulating anabolic and catabolic cell processes and inflammatory responses, ultimately suppressing OA in mouse and human knee cartilage. These results demonstrate that GA-017's activation of YAP/TAZ has significant potential in the treatment of OA and further suggest that drug-induced activation of YAP/TAZ is a feasible approach for treating OA.