Details

Autor(en) / Beteiligte

• Chang, Lan‐Yun
• Lai, Chao‐Han
• Kuo, Cheng‐Hsiang
• Chang, Bi‐Ing
• Wu, Hua‐Lin
• Cheng, Tsung‐Lin

Titel

Recombinant thrombomodulin lectin‐like domain attenuates Porphyromonas gingivalis lipopolysaccharide‐induced osteoclastogenesis and periodontal bone resorption

Ist Teil von

• Journal of periodontology (1970), 2021-11, Vol.92 (11), p.1622-1634

Ort / Verlag

United States

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• Background Evidence demonstrates that the thrombomodulin (TM) lectin domain (TMD1) exerts anti‐inflammatory functions. Lipopolysaccharides derived from Porphyromonas gingivalis (Pg‐LPS) are considered a major pathogenic factor for chronic periodontitis, promoting inflammation, osteoclastogenesis and alveolar bone resorption. Herein, we aimed to evaluate the potential therapeutic effect of recombinant TMD1 (rTMD1) in suppression of Pg‐LPS‐induced osteoclastogenesis and periodontal bone loss. Methods In vitro, the effects of Pg‐LPS, tumor necrosis factor (TNF)‐α and rTMD1 on osteoclast differentiation were investigated using receptor activator of nuclear factor‐κB ligand (RANKL)‐stimulated RAW 264.7 macrophages. In vivo, the effects of rTMD1 treatment were evaluated in a model of experimental periodontitis induced by direct injection of Pg‐LPS into the vestibular gingiva. Results Administration of Pg‐LPS to RANKL‐stimulated RAW 264.7 macrophages resulted in upregulation of CD86 and osteoclast marker (eg, Dc‐stamp and Trap) gene expression and increase of pro‐inflammatory cytokine production (e.g., TNF‐α) during osteoclast differentiation, and rTMD1 can attenuate these effects. Also, rTMD1 inhibited Pg‐LPS‐enhanced in vitro bone resorption in a dose‐dependent manner. Moreover, TNF‐α promoted phosphorylation of p38 and ERK during osteoclast differentiation, and the signal activation can be inhibited by rTMD1. Finally, treatment with rTMD1 hindered Pg‐LPS‐induced alveolar bone loss in experimental periodontitis in mice. Conclusion Our study demonstrated that rTMD1 attenuates Pg‐LPS‐enhanced M1 macrophage polarization, osteoclastogenesis and periodontal bone resorption and thus holds therapeutic promise for periodontitis.