Periodontal ligament‐associated protein‐1 promotes osteoclastogenesis in mice by modulating TGF‐β1/Smad1 pathway

Abstract Background Periodontal ligament‐associated protein‐1 (PLAP‐1), an important target molecule of osteoarthritis research, may affect alveolar bone resorption. The aim of our study was to comprehensively and systematically detect the effect of PLAP‐1 on alveolar bone resorption and the underlying mechanism in PLAP‐1 knockout mouse models. Methods We used a PLAP‐1 knockout (C57BL/6N‐ Plap‐1 −/− ) mouse model to investigate the effect of PLAP‐1 on osteoclast differentiation and the underlying mechanism by adding Porphyromonas gingivalis lipopolysaccharide to stimulate bone marrow‐derived macrophages. The effect of PLAP‐1 on alveolar bone resorption and the underlying mechanism were studied using a ligature periodontitis model, with microcomputed tomography imaging, immunochemistry, and immunofluorescence. Results The in vitro analysis results demonstrated that PLAP‐1 knockout significantly inhibited osteoclast differentiation under both normal and inflammatory conditions. Bioinformatic analysis, immunofluorescence, and co‐immunoprecipitation showed colocalization and interaction between PLAP‐1 and transforming growth factor beta 1 (TGF‐β1). The phosphorylation of Smad1 was reduced in the PLAP‐1 knockout cells compared with that in the cells from wild‐type mice. The in vivo analysis results demonstrated that PLAP‐1 knockout decreased bone resorption and the levels of osteoclast differentiation markers in experimental periodontitis compared with those in wild‐type mice. Immunofluorescence staining confirmed colocalization of PLAP‐1 and TGF‐β1 in the experimental periodontitis model. The phosphorylation level of Smad1 was significantly reduced in PLAP‐1 knockout mice compared with that in wild‐type mice. Conclusions This study revealed that the knockout of PLAP‐1 inhibits osteoclast differentiation and decreases alveolar bone resorption through the TGF‐β1/Smad1 signaling pathway, which could serve as an innovative target for the prevention and treatment of periodontitis.