M6a Demethylation Promotes Alveolar Bone Resorption In Apical Periodontitis

The aim of this study was to investigate the role of m6A methylation in the process of alveolar bone resorption and osteoclast formation in apical periodontitis and explored its regulatory mechanism. The rat apical periodontitis model and osteoclast model were established. The m6A levels during alveolar bone resorption and osteoclastogenesis were detected by dot-blot. The expression of m6A demethylase FTO was detected by WB and qPCR assays. The effect of FTO on osteoclastogenesis and alveolar bone resorption was confirmed by knockdown of FTO by lentiviral shRNA or treatment with FTO inhibitor Dac51. The total m6A level was significantly reduced in both alveolar bone tissue of rat apical periodontitis model and osteoclasts, accompanied by a significant increase in the expression of m6A demethylase FTO. Knockdown of FTO by shRNA transfection or treatment with FTO inhibitor Dac51, both decreased FTO expression in osteoclasts, down-regulated the expression of NFATc1, MMP9 and CTSK, inhibited osteoclastogenesis and its bone resorption function. During alveolar bone resorption and osteoclastogenesis, the m6A demethylase FTO is upregulated, enhancing the expression of NFATc1, MMP9, and CTSK to drive osteoclast formation and exacerbate bone loss in apical periodontitis.