PTH Promotes Chondrogenesis of Fibrocartilage Stem Cells and Alleviates Temporomandibular Joint Osteoarthritis

PTH促进纤维软骨干细胞的软骨生成并缓解颞下颌关节骨关节炎

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PTH promotes the proliferation and chondrogenic differentiation of condylar FCSCs.

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