The temporomandibular joint (TMJ) disc is a biconcave cushion located between the glenoid fossa and the mandibular condyle that is subjected to routine movement stimuli [1]. Based on its relative intracorporeal position, the TMJ disc is conventionally divided into three bands, and sometimes even nine [2,3]. The intermediate band consists of region-dependent collagen fibers aligned in the anteroposterior orientation, while the anterior and posterior bands contain collagen fibers with a circumferential orientation [4]. When the intermediate fiber groups reach the peripheral ring, these fibers assemble into a structurally transitional region, where they become confluent and form a reticular net-like structure [5]. In the present study, based on the orientation of the collagen fibers, we separated the TMJ disc into three regions: peripheral region (PR), intradiscal junction (IJ), and central region (CR).

As exemplified by tendon enthesis or the meniscal attachment, the transitional structural and mechanical characteristics at the junctional regions within the human body are designed to ensure flexible connections for efficient stress transmission and stability [[6], [7], [8]]. The junction can adapt to mechanical demands by nanoscale denaturation, microscale load-sharing, and macroscale energy balancing [9]. However, while withstanding repetitive mechanical stimuli, the junction may incur overuse injuries and undergo changes in the collagen hierarchy [10]. While the temporomandibular IJ shares functional similarities with other attachment sites, few studies have focused on its specific structural and mechanical characteristics.

TMJ osteoarthritis (TMJOA) is a chronic degenerative disease characterized by progressive degradation of the TMJ disc and condyle [11]. While the cytobiology and mechanobiology of the condyle have been extensively studied, the change that occur within the TMJ disc remain relatively unexplored [[12], [13], [14]]. However, it is essential to understand the discal pathogenesis. Clinical studies have found that the position of the IJ within the TMJ disc is a vulnerable area before orthognathic and joint surgery [15]. Given the clinical evidence, we hypothesized that the degeneration of the IJ was one of the earliest events seen in the initiation of discal pathogenesis.

The present study aimed to elucidate the role of the IJ in the initiation and progression of discal pathogenesis. To determine whether the degeneration of the IJ is the initial event or the final outcome in discal pathogenesis, we first compared the morphological structure of the IJ in different species to prove universality. Specifically, we analyzed rabbit models of anterior disc displacement (ADD)-mediated TMJOA model and ADD with reduction (ADDwR), one of the most widely used models for studying discal pathogenesis in vivo [16,17]. Using the ADD model, we recently showed that the diameters of collagen fibrils are decreased at 20-week post-surgery [18]. Building on this work, the present study used high-resolution microscopy and indentation to develop an atlas of the structural and mechanical changes within the IJ from 1-week to 8-week after surgery. Furthermore, by dissecting normal and 1-week postoperative IJs for mass spectrometry proteomics, we discovered the mechanical-related protein responsible for the mechanism of the pathogenesis.