PTHrP promotes subchondral bone formation in TMJ-OA  

作　　者：Jun Zhang Caixia Pi Chen Cui Yang Zhou Bo Liu Juan Liu Xin Xu Xuedong Zhou Liwei Zheng 

机构地区：[1]State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology,Sichuan University,Chengdu,China [2]Yunnan Key Laboratory of Stomatology,Kunming,China [3]Department of,Affiliated Stomatological Hospital,Kunming Medical University,Kunming,China

出　　处：《International Journal of Oral Science》2022年第4期489-496,共8页国际口腔科学杂志（英文版）

基　　金：NSFC grant(82170921,81771033);the Department of Science and Technology of Sichuan Province(2016JQ0054)to L.Z.;The Yunnan Provincial Department of Science and Technology-Kunming Medical University granted a basic research joint special fund project(202001AY070001-151)to J.Z.

摘　　要：PTH-related peptide(PTHr P) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHr P and transforming growth factor-β(TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion. TMJ-OA model animals administered intermittent PTHr P(i PTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT,histomorphometry, and Western Blot analyses disclosed that i PTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, i PTH increased the number of osterix(OSX)-positive cells and osteocalcin(OCN)-positive cells in the subchondral bone marrow cavity. However, the number of osteoclasts was also increased by i PTH, indicating that subchondral bone volume increase was mainly due to the i PTH-mediated increase in the bone-formation ability of condylar subchondral bone.In vitro, PTHr P treatment increased condylar subchondral bone marrow-derived mesenchymal stem cell(SMSC) osteoblastic differentiation potential and upregulated the gene and protein expression of key regulators of osteogenesis. Furthermore, we found that PTHr P-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggested that i PTH improves OA lesions by enhancing osteoblastic differentiation in subchondral bone and suppressing aberrant active TGFβsignalling. These findings indicated that PTHr P, which targets the TGFβ signalling pathway, may be an effective biological reagent to prevent and treat TMJ-OA in the clinic.

关 键 词：TMJ DEGENERATION OCCLUSION 

分 类 号：R781[医药卫生—口腔医学]