Heterogeneity and Fate Regulation of Fibrocartilage Stem Cells

The temporomandibular joint (TMJ) is one of the most complex and most frequently used synovial joints. The condylar surface is covered by a distinctive type of fibrocartilage that possesses a remarkable capacity for adaptive remodeling. In recent years, with rapid advances of single-cell transcriptomics and in vivo lineage-tracing technologies, fibrocartilage stem cells (FCSCs) residing in the superficial layer of the mandibular condyle have been demonstrated to play a decisive role in TMJ development, homeostasis, and the pathological progression of temporomandibular joint osteoarthritis (TMJOA). However, FCSCs do not constitute a single homogeneous population but rather exhibit substantial lineage heterogeneity. Under the spatiotemporal orchestration of distinct mechanical microenvironments and molecular signaling networks, different subpopulations of stem/progenitor cells adopt divergent fate trajectories toward chondrogenic or osteogenic differentiation. This review focuses on the cellular heterogeneity of FCSCs and the regulatory mechanisms governing their fate determination, summarizing recent advances in the field and discussing the translational potential of these findings for TMJ regenerative medicine and targeted therapeutic strategies.