Role of YAP/TAZ Mechanobiological Signaling in Osteoporosis and Osteoarthritis.

Abstract

Osteoporosis and osteoarthritis are prevalent degenerative bone diseases characterized by the deterioration of bone structure and function. Mechanical signals play a crucial role in their pathogenesis by modulating cellular behavior and tissue homeostasis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key transcriptional regulators of the Hippo pathway, act as critical mechanosensors that translate mechanical cues into osteocyte and chondrocyte responses. Specifically, YAP/TAZ regulate osteocyte lacunar-canalicular remodeling, chondrocyte mechanoadaptation, and extracellular matrix metabolism, driving bone and cartilage degeneration when dysregulated. Historically, the Hippo pathway was initially linked to organ size control, but recent advances highlight its central role in skeletal mechanobiology. This narrative review elucidates YAP/TAZ-mediated mechanobiological signaling in osteoporosis and osteoarthritis, examining their roles in osteocyte differentiation, apoptosis, and tissue repair. We analyze associated molecular networks and aberrant expressions in disease, emphasizing the therapeutic potential of targeting YAP/TAZ for stage-specific interventions, such as promoting bone formation or inhibiting cartilage breakdown.