Cartilage and Subchondral Bone Degradation of Anterior Disc Displacement Mice

Objectives: This study aims to explore the cell fate and functional changes of fibrocartilage stem cells (FCSCs) during the process of temporomandibular joint (TMJ) cartilage and subchondral bone destructions caused by unilateral anterior disc displacement (ADD).
Methods: Surgically induced ADD mouse model was generated in 4-week-old C57/B6 male mice. For FCSCs lineage tracing in TMJ, Gli1-CreER⁺; ROSA-tdTomato^fl/fl mice were used and tamoxifen were intraperitoneally injected 48 hours before ADD surgery. 1/2/4/8 weeks after ADD model generation, mice TMJs were dissected for analyses. H&E, Safranine O and immunofluorescent staining were performed for observing histological and molecular changes during ADD pathological changes. Modified Mankin score was used to analyze cartilage damage degrees in TMJ. Micro-CT analyses were performed quantify subchondral bone loss and structural changes at the later stages of ADD TMJ.
Results: Compared to Sham groups, the TMJ cartilage in ADD mice exhibited progressively aggravated osteoarthritis (OA) changes, including gross morphological changes of condylar head, disarranged cell distribution in multiple cartilage layers, interrupted chondrogenic differentiation and extracellular matrix secretion, as well as subchondral bone loss and reconstruction. More importantly, the lineage tracing experiment showed that Gli1⁺ FCSCs were activated at 1week in ADD mouse model with increased proliferation in the superficial layer evaluated by Edu staining and elevated chondrogenic differentiation characterized by tdTomato⁺/ SOX9⁺ cells. At 4 weeks of ADD, both proliferation and chondrogenic translation were disrupted in ADD group. Besides, Gli1⁺ FCSCs effected by ADD showed different molecular biological alterations in medial and posterior regions of condyle cartilage.
Conclusions: Surgical ADD in mice induced TMJ osteoarthritis phenotype aggravating with time, including the degeneration of TMJ cartilage and loss of subchondral bone. FCSCs In TMJ were activated during early process of ADD, while the proliferation and chondrogenic capacity of FCSCs were interfered at later stage of ADD in mice.