The essential role of yes-associated protein (YAP) in the regulation of chondrocyte and cartilage degeneration

Abstract Osteoarthritis (OA) is a chronic degenerative joint disease that significantly impacts the quality of life in aging patients. The primary pathological features of OA include the destruction and degeneration of cartilage tissue, which result from chondrocyte apoptosis and metabolic imbalances in the extracellular matrix (ECM). The Hippo signaling pathway and its primary downstream effector, Yes-associated protein (YAP), have recently emerged as crucial regulators of chondrocyte function and cartilage homeostasis. However, the precise pathogenesis of OA remains unclear. Therefore, understanding the underlying molecular mechanisms of cartilage degeneration and identifying potential drug targets for OA treatment is crucial. Evidence suggests that Yes-associated protein (YAP), the principal downstream effector of the Hippo pathway, plays a pivotal role in regulating chondrocyte behavior, phenotype, and cartilage metabolism, thereby significantly influencing OA. This review emphasizes the role of YAP in chondrocyte differentiation and proliferation, matrix metabolism, and biomechanics. Additionally, we comprehensively discuss the impact of YAP on cartilage metabolism and the progression of OA, with a focus on its context-dependent functions and therapeutic potential.