Occlusal abnormalities and temporomandibular joint osteoarthritis: A narrative review of cross-scale mechanical-metabolic-immune mechanisms.

OBJECTIVE

To synthesize recent multiscale evidence and propose a unified mechanical-metabolic-immune framework for the role of occlusal abnormalities in temporomandibular joint osteoarthritis (TMJOA) pathogenesis.

DESIGN

A narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for English-language articles published between January 2011 and April 2026. Search terms combined concepts related to temporomandibular joint osteoarthritis, malocclusion or occlusal abnormalities, mechanotransduction, Piezo1, integrin signaling, mitochondrial dysfunction, cGAS-STING activation, single-cell transcriptomics, macrophages, and sexual dimorphism. Clinical, imaging, animal, cellular, omics-based, and mechanistic studies relevant to TMJOA were narratively synthesized.

RESULTS

Occlusal abnormalities may alter mandibular kinematics and joint stress distribution, thereby activating mechanotransduction through Piezo1, integrins, and related developmental feedback loops. Sustained mechanical overload may promote calcium dysregulation, endoplasmic reticulum stress, mitochondrial dysfunction, and activation of the cGAS-STING pathway. These changes can shift cellular metabolism toward increased glycolysis and contribute to a pro-inflammatory microenvironment. Single-cell and lineage-tracing evidence further suggests that sex-related immune regulation, including macrophage ontogeny and Xist-associated inflammatory responses, may contribute to the female predominance of temporomandibular joint disorders, although TMJ-specific validation remains needed.

CONCLUSIONS

TMJOA progression can be interpreted as a cross-scale process in which abnormal occlusal loading links biomechanical stress, metabolic dysfunction, and immune remodeling. These pathways may represent potential targets for future mechanism-based diagnosis and therapy.