Yue Zhihang, Gong Wuyi, Chu Haojun, Li Yongming
Shanghai Engineering Research Center of Tooth Restoration and Regeneration and Tongji Research Institute of Stomatology and Department of Orthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, 200072, China.
Tissue Eng Regen Med. 2025 Jun 16. doi: 10.1007/s13770-025-00723-y.
Parathyroid hormone (PTH) can promote subchondral bone formation and alleviate temporomandibular joint (TMJ) osteoarthritis (OA), but the effects of PTH on fibrocartilage stem cells (FCSCs) in cartilage surfaces have yet to be studied.
We established the TMJOA model in rats and administered PTH to treat them. Rat condyles were analyzed using micro-computed tomography, histological, and immunohistochemical staining. To study PTH's effects on FCSCs in vitro, we employed quantitative polymerase chain reaction, Western Blot, and immunofluorescence staining. We also constructed the TMJOA model in tdTomato; Cathepsin K (Ctsk)-Cre mice and rescued them with PTH. EdU and immunofluorescence staining were used to measure the proliferation and chondrogenic differentiation of FCSCs in vivo. Furthermore, after discectomy, we injected diphtheria toxin (DT) into the Ctsk-Cre; diphtheria toxin receptor (DTR) mice to ablate FCSCs. Afterwards, PTH was injected, and we evaluated the Collagen Type II Alpha 1 (COL2A1)-positive area using immunofluorescence staining.
We successfully developed a TMJOA model, and after treatment with PTH, the rat condyles' BV/TV and Tb. Th increased, and the expression of chondrogenic-related genes was elevated. Additionally, PTH promoted the chondrogenic differentiation of FCSCs in vitro. In tdTomato; Ctsk-Cre mice, the Ctsk/EdU and Ctsk/COL2A1 double-positive cells were increased after PTH administration. Moreover, after the ablation of FCSCs by DT, the effects of PTH treatment were notably reduced.
PTH promotes the proliferation and chondrogenic differentiation of condylar FCSCs.
甲状旁腺激素（PTH）可促进软骨下骨形成并减轻颞下颌关节（TMJ）骨关节炎（OA），但PTH对软骨表面纤维软骨干细胞（FCSCs）的影响尚未得到研究。
我们在大鼠中建立了TMJOA模型并用PTH进行治疗。使用显微计算机断层扫描、组织学和免疫组织化学染色对大鼠髁突进行分析。为了在体外研究PTH对FCSCs的影响，我们采用了定量聚合酶链反应、蛋白质免疫印迹和免疫荧光染色。我们还在tdTomato；组织蛋白酶K（Ctsk）-Cre小鼠中构建了TMJOA模型并用PTH进行挽救。使用EdU和免疫荧光染色在体内测量FCSCs的增殖和软骨形成分化。此外，椎间盘切除术后，我们向Ctsk-Cre；白喉毒素受体（DTR）小鼠注射白喉毒素（DT）以消融FCSCs。之后，注射PTH，我们使用免疫荧光染色评估II型胶原α1（COL2A1）阳性区域。
我们成功建立了TMJOA模型，用PTH治疗后，大鼠髁突的骨体积分数（BV/TV）和骨小梁厚度（Tb.Th）增加，软骨形成相关基因的表达升高。此外，PTH在体外促进了FCSCs的软骨形成分化。在tdTomato；Ctsk-Cre小鼠中，给予PTH后Ctsk/EdU和Ctsk/COL2A1双阳性细胞增加。此外，DT消融FCSCs后，PTH治疗的效果显著降低。
PTH促进髁突FCSCs的增殖和软骨形成分化。
