Overloading stress-induced progressive degeneration and self-repair in condylar cartilage

Overloading stress-induced condylar cartilage degeneration acts as the main pathologic change in temporomandibular joint osteoarthritis (TMJ-OA). However, the progression of degeneration and the ability for self-repair remain poorly understood. Here, we explored the progression of cartilage degeneration by dividing pathological stages using a steady mouth-opening mouse model. Then, we observed changes of cartilage by removing the loading at different stages to test the potential self-repair after degeneration induced. Three-dimensional confocal microscopy combined with histology and micro-CT scanning was applied to examine TMJ at different stages of degeneration before and after self-repair. We found the cartilage underwent progressive and thorough degeneration as the overloading stress developed. During the initial adaptation stage, robust proliferation of posteromedial cartilage began at the area of direct loading. Subsequently, widespread chondrocyte apoptosis was found, followed by new chondrocyte proliferation in aggregates with matrix degradation and subchondral bone catabolism. Finally, with cartilage surface damage, the degeneration reached a point where the lesion could not be reversed by self-repair. While the cartilage nearly returned to normal when the interference was removed within 5 days. These results suggested overloading force induces a pathological process of successive degeneration in TMJ cartilage, which can be reversed by self-repair at early stages.