Regulation of osteoclast differentiation and inflammatory signaling by TCF8 in periodontitis

Abstract Objectives The aim of this study was to explore the potential role of zinc‐finger homeodomain transcription factor (TCF8) in osteoclastogenesis and inflammation during periodontitis. Materials and Methods Rats with periodontitis were induced via Porphyromonas gingivalis ‐lipopolysaccharide (Pg‐LPS) injection. The recombinant lentivirus delivering short hairpin RNA (shRNA) against TCF8 was used to downregulate TCF8 in vivo. Alveolar bone loss in rats was determined by micro‐computed tomography (Micro‐CT). Typical pathological changes, periodontal tissue inflammation, and osteoclastogenesis were evaluated via histological analyses. The RAW264.7‐derived osteoclasts were induced by RANKL stimulation. TCF8 downregulation in vitro was achieved by lentivirus infection. The osteoclast differentiation and inflammatory signaling in RANKL‐induced cells were measured via immunofluorescence methods and molecular biology approaches. Results Porphyromonas gingivalis ‐lipopolysaccharide induced rats exhibited overexpressed TCF8 in their periodontal tissues, while TCF8 knockdown attenuated the bone loss, tissue inflammation, and osteoclastogenesis in LPS‐induced rats. Besides, TCF8 silencing inhibited RANKL‐induced osteoclast differentiation in RAW264.7 cells, as evidenced by the reduced numbers of TRAP‐positive osteoclasts, less formation of F‐actin rings, and downregulated expressions of osteoclast‐specific markers. It also exerted an inhibitory effect on the NF‐κB signaling in RANKL‐induced cells via blocking NF‐κB p65 phosphorylation and nuclear translocation. Conclusions TCF8 silencing inhibited alveolar bone loss, osteoclast differentiation, and inflammation in periodontitis.