Regulation of chondrocyte apoptosis in osteoarthritis by endoplasmic reticulum stress.

Abstract

Osteoarthritis(OA), a common degenerative joint disease, is characterized by the apoptosis of chondrocytes as a primary pathophysiological change, with endoplasmic reticulum stress(ERS) playing a crucial role. It has been demonstrated that an imbalance in endoplasmic reticulum(ER) homeostasis can lead to ERS, activating three cellular adaptive response pathways through the unfolded protein response(UPR) to restore ER homeostasis. Mild ERS exerts a protective effect on cells, while prolonged ERS that disrupts the self-regulatory balance of the endoplasmic reticulum activates apoptotic signaling pathways, leading to chondrocyte apoptosis and hastening OA progression. Hence, controlling the ERS signaling pathway and its apoptotic factors has become a critical focus for preventing and treating OA. This review aims to elucidate the key mechanisms of ERS pathway-induced apoptosis, associated targets, and regulatory pathways, offering valuable insights to enhance the mechanistic understanding of OA. And it also reviews the mechanisms studied for ERS-related drugs or compounds for the treatment of OA.