AN INTEGRATED MECHANOBIOLOGICAL FRAMEWORK LINKING MECHANICAL LOADING TO TISSUE DEGENERATION IN TEMPOROMANDIBULAR JOINT OSTEOARTHRITIS

Abstract

Temporomandibular joint osteoarthritis (TMJOA) is a complex degenerative condition involving the coordinated interaction of mechanical loading, cellular mechanotransduction, inflammation, extracellular matrix degradation, and osteochondral remodeling. The traditional concept of TMJOA as a consequence of simple mechanical “wear and tear” does not fully explain the dynamic biological responses of the joint tissues. This thesis presents an integrated mechanobiological framework linking pathological mechanical loading to tissue degeneration across the condylar fibrocartilage, subchondral bone, osteochondral interface, synovium, and articular disc. Excessive compression and shear may activate mechanosensitive pathways, particularly PIEZO1-mediated calcium signaling, while alterations in focal adhesion kinase and NG2/CSPG4-associated signaling contribute to extracellular matrix disruption. Mechanical stress may further induce mitochondrial dysfunction, oxidative stress, inflammatory signaling, and activation of matrix-degrading enzymes. In the subchondral bone, abnormal loading is associated with osteoclastogenesis and activation of pathways including RANTES–CCR–Akt2, whereas matrix stiffening may stimulate Plexin-B2/YAP–SLIT3 signaling and angiogenic remodeling. Damage-associated molecular patterns and inflammatory mediators may amplify these mechanical signals through immuno-mechanical crosstalk. Collectively, these mechanisms support a whole-joint model in which mechanical stress is translated into cellular and molecular responses that progressively alter cartilage, bone, synovium, and disc integrity. The proposed framework may provide a conceptual basis for future mechanobiological phenotyping, multimodal imaging, biomarker research, and individualized risk stratification in TMJOA.