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 · 发表于：International Journal of Oral Science · 年份：2022 · DOI：10.1038/s41368-022-00189-x · 被引用次数：32 · 研究领域：Bone health and treatments、Osteoarthritis Treatment and Mechanisms、Head and Neck Cancer Studies

PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP 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 PTHrP (iPTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT, histomorphometry, and Western Blot analyses disclosed that iPTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, iPTH 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 iPTH, indicating that subchondral bone volume increase was mainly due to the iPTH-mediated increase in the bone-formation ability of condylar subchondral bone. In vitro, PTHrP 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 PTHrP-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggeste...