TIFA contributes to periodontitis in diabetic mice via activating the NF?κB signaling pathway

Diabetic periodontitis (DP) refers to destruction of periodontal tissue and absorption of bone tissue in diabetic patients. Tumor necrosis factor receptor?associated factor (TRAF)?interacting protein with forkhead?associated domain (TIFA) as a crucial regulator of inflammation activates the NF?κB signaling pathway to regulate cell biological behavior. However, the function and mechanism of TIFA on DP suffer from a lack of research. In the present study, TIFA was upregulated in the periodontal tissue of a DP mouse model. In addition, the expression of TIFA in RAW264.7 cells was induced by high glucose (HG) culture and increased by lipopolysaccharide (LPS) from Porphyromonas?gingivalis treatment in a time?dependent manner. Knockdown of TIFA significantly reduced the levels of inflammatory cytokines, including TNF?α, IL?6, IL?1β and monocyte chemoattractant protein?1, in HG and LPS?induced RAW264.7 cells. The nuclear translocation of NF?κB p65 was induced by HG and LPS and was clearly suppressed by absence of TIFA. The expression of downstream factors Nod?like receptor family pyrin domain?containing 3 and apoptosis?associated speck?like protein was inhibited by silencing TIFA. Moreover, TIFA was increased by receptor activator of NF?κB (RANK) ligand (RANKL) in a concentration dependent manner. The expression of cathepsin K, MMP9 and nuclear factor of activated T cells cytoplasmic 1 was downregulated by depletion of TIFA. RANKL?induced osteoclast differentiation was inhibited by silencing of TIFA. Meanwhile, the decrease of TIFA blocked activation of the NF?κB pathway in RANKL?treated RAW264.7 cells. In conclusion, TIFA as a promoter regulates the inflammation and osteoclast differentiation via activating the NF?κB signaling pathway.

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