Early collagen degeneration in the temporomandibular intradiscal junction portends the onset of discal pathogenesis

The temporomandibular intradiscal junction is a structural transition region connecting anteroposterior and circumferential aligned collagens fibers in the temporomandibular joint disc. Despite inherent stiffness, this region is incredibly susceptible to perforation under pathological conditions. This study aimed to determine whether the intradiscal junction was the initiation destructive site for discal degeneration. Utilizing high-resolution microscopy and nanoindentation, we characterized the structural and mechanical properties of the intradiscal junction. In rabbit models of anterior disc displacement-mediated temporomandibular osteoarthritis, we observed a significant reduction in collagen fibril diameter and an increase in denatured procollagen within the intradiscal junction as early as one week post-surgery, further spreading across the whole disc. Mass spectrometry proteomics showed that the alteration of the intradiscal junction was the consequence of mechanical stimuli mediated by tenascin-C and metalloproteinase-3. Notably, these degenerative changes were blocked by early reduction of the discal position. In vitro monotonic loading confirmed the dominant contribution of the intradiscal junction to the overall mechanical function of the disc. The present findings underscore the pivotal role of the intradiscal junction in the pathogenesis of discal degeneration, providing early detection indicators and therapeutics. STATEMENT OF SIGNIFICANCE: Temporomandibular joint osteoarthritis (TMJOA) is a prevalent disorder affecting the structure and mechanics of the TMJ disc, with no effective early detection or treatment strategies. This study identifies the temporomandibular intradiscal junction (IJ) as the site where discal pathogenesis begins. Degeneration at the IJ involves reduced collagen fibril diameter and denatured procollagens, compromising the mechanical properties of the entire disc. Rescuing the IJ's position through TMJ anchorage surgery may restore mechanosensitive homeostasis and prevent further discal degeneration. These findings highlight the importance of the IJ in the discal progression, payving the way for early detection methods and treatment strategies that target aberrant remodeling in this critical region to slow or reverse disease.