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Updated: Jul 23, 2025
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Periodontal ligament-associated protein-1 promotes osteoclastogenesis in mice by modulating TGF-β1/Smad1 pathway
Shuang Liu1, Xijiao Yu2, Qiushuang Guo1
1Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China.
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.
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