Endoplasmic reticulum stress as a nexus of temporomandibular joint osteoarthritis

This review aims to summarize the molecular architecture of endoplasmic reticulum (ER) stress signaling networks and their mechanistic involvement in temporomandibular joint osteoarthritis (TMJOA) progression, and current therapeutic strategies targeting ER stress mediators and the obstacles from bench to bedside.

The related literatures of the roles of ER in TMJOA were searched through PubMed database by different combinations of the following keywords including animal models, ER, unfolded protein response (UPR), ER-associated degradation (ERAD), ER-phagy, TMJ, and OA. No filters were used in the search. The references of eligible studies were also analyzed and reviewed comprehensively.

This review discussed how ER stress signaling orchestrated TMJOA pathogenesis, including UPR, ERAD, and ER-phagy. It was also summarized how biomechanical stress and hypoxic microenvironment synergistically exacerbated ER stress, and the current therapeutic strategies for TMJOA based on ER stress modulators and the obstacles in bench-to-bedside research.

ER proteostasis represented a pivotal but underexplored therapeutic axis in TMJOA. Bridging the gap between mechanistic understanding of ER stress adaptation and TMJ-specific pathobiology is essential for developing novel therapeutic strategies for TMJOA.