State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Osteoarthritis Cartilage. 2020 Jun;28(6):842-852. doi: 10.1016/j.joca.2020.02.835. Epub 2020 Mar 6.
This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing.
Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface.
hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFP FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients.
We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders.
本研究旨在鉴定人纤维软骨干细胞（hFCSCs）的居住位置，表征其干细胞特性，并研究调节软骨稳态和修复过程中纤维软骨干细胞（FCSCs）向软骨分化的功能机制。
分析 hFCSCs 和人颌面部间充质干细胞（hOFMSCs）的细胞学特征。比较 hFCSCs 与 hOFMSCs 的体外和体内软骨形成潜能。通过 shRNA 干扰体外研究 SOX9 在 FCSCs 软骨形成中的调节作用，并通过 GFP FCSCs 处理大鼠髁突软骨缺损模型。还检查了 SOX9 在颞下颌关节骨关节炎（TMJOA）患者软骨表面的表达。
hFCSCs 表现出典型的间充质干细胞特征，与 hOFMSCs 相比，具有显著更强的软骨形成能力。此外，hFCSCs 显示出明显增加的 SOX9 表达。在软骨小球培养中，hFCSCs 的 SOX9 表达强于 hOFMSCs。SOX9 shRNA 干扰体外下调 hFCSCs 的软骨形成能力，以及破坏 GFP FCSCs 向成熟软骨细胞的迁移和软骨分化在大鼠髁突软骨缺损中。值得注意的是，在 TMJOA 患者的髁突表面区也发现 SOX9 表达受到抑制。
我们发现 FCSCs 存在于人 TMJ 软骨中，并对其独特的干细胞特征进行了表征。SOX9 对 hFCSCs 的软骨分化至关重要，全面了解 SOX9 在 hFCSCs 中的调节作用对于探索 TMJ 紊乱期间髁突软骨降解的潜在干预策略非常重要。
