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

Abstract

BackgroundPeriodontal 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 detect the effect of PLAP‐1 comprehensively and systematically on alveolar bone resorption and the underlying mechanism in PLAP‐1‐knockout mouse models.MethodsWe 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 micro‐computed tomography imaging, immunochemistry, and immunofluorescence.ResultsThe 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. The phosphorylation level of Smad1 was significantly reduced in PLAP‐1 knockout mice compared with that in wild‐type mice.ConclusionsThis study revealed that the knockout of PLAP‐1 inhibits the osteoclast differentiation and decreases alveolar bone resorption through the TGF‐β1/Smad1 signaling pathway, which could serve an innovative target for the prevention and treatment of periodontitis.This article is protected by copyright. All rights reserved

The role of autophagy in odontogenesis, dental implant surgery, periapical and periodontal diseases

“…59 Knocking down Periodontal ligamentassociated protein-1 has been shown to hinder osteoclast development and decrease alveolar bone resorption via the TGF-β1/ Smad1 signalling pathway. 62 This results suggest that high TGF-β1 may be a protective factor for periodontitis, given that it accelerates connective tissue remodelling and cell differentiation. Various investigations across different organs have demonstrated a direct relationship between activated autophagy and MFb development in tissue regeneration.…”

“…In a study, TGF‐ β1 levels were found to be high in patients with chronic periodontitis 59 . Knocking down Periodontal ligament‐associated protein‐1 has been shown to hinder osteoclast development and decrease alveolar bone resorption via the TGF‐β1/Smad1 signalling pathway 62 . This results suggest that high TGF‐β1 may be a protective factor for periodontitis, given that it accelerates connective tissue remodelling and cell differentiation.…”