Regulated cell death in the temporomandibular joint: From disc internal derangement to osteoarthritis and tissue repair.

OBJECTIVE

This narrative review examines regulated cell death programmes underlying disc internal derangement and condylar osteoarthritis in the temporomandibular joint (TMJ), evaluating the balance between cell loss and endogenous repair capacity across both compartments.

DESIGN

A narrative, mechanism-oriented review of PubMed-indexed literature, supplemented by citation tracking from core TMJ cell death studies, with evidence stratified by an explicit hierarchy prioritising human TMJ tissue and synovial fluid findings over animal, in vitro, and non-TMJ osteoarthritis data.

RESULTS

In the disc, internal derangement is associated with apoptosis via extrinsic TRAIL/DR5/caspase-3 and intrinsic Bax/cytochrome c/caspase-9 pathways; chondrocyte-like apoptosis appears repair-limiting, whereas the CD34 + perivascular stromal niche may serve as a local repair reservoir. In condylar cartilage and synovium, necroptosis, pyroptosis and ferroptosis interact with autophagy dysregulation and senescence-related mitochondrial dysfunction in TMJ osteoarthritis (TMJOA), through overlapping mechanisms involving mechanical stress, inflammatory cytokines, oxidative injury, iron loading and altered vesicular communication. A PANoptosis-compatible model is proposed, in which caspase-3, GSDMD/caspase-1, and RIPK3/MLKL signalling may converge in inflamed TMJ tissues, though direct demonstration of a PANoptotic complex remains required.

CONCLUSIONS

Regulated cell death in the TMJ is compartment-specific and repair-coupled rather than uniformly degenerative. Distinguishing death programmes and repair reservoirs in the disc versus condylar cartilage offers a framework for pathway-specific and multi-pathway therapeutic targeting in future studies.