MicroRNA-155-3p Mediates TNF-α-Inhibited Cementoblast Differentiation

Periodontitis is a prevalent and chronic inflammatory disease that is interrelated with systemic health. periodontitis can be promoted by tumor necrosis factor α (tnf-α). cementum,a vital part of the periodontium,is a bone-like mineralized tissue that is produced by cementoblasts. our laboratory previously revealed that tnf-α inhibits cementoblast differentiation and mineralization. however,how tnf-α modulates cementoblast differentiation and mineralization remains largely unknown. microrna-155 (mir-155) is induced and regulates tnf-α-inhibited osteogenic differentiation. in this study,we found that mir-155-3p was increased during tnf-α-stimulated occm-30 cells and involved in cementoblast differentiation and mineralization. overexpression of mir-155-3p suppressed cementoblast mineralization. bioinformatics analysis revealed that potassium channel tetramerization domain containing 1 (kctd1) is a candidate target gene of mir-155-3p. moreover,mir-155-3p overexpression suppressed kctd1 levels. meanwhile,its knockdown increased kctd1 expression. transfection with mir-155-3p also inhibited the luciferase activity of 3′-untranslated regions in the kctd1 wild type but not the mutant. these data indicated that kctd1 is a direct and novel target of mir-155-3p. the wnt signaling pathway inhibits cementoblast differentiation,and we further demonstrated that mir-155-3p partially modulates cementoblast differentiation through the canonical wnt signaling pathway. in addition to the gain/loss function assay of mir-155-3p,the luciferase activity assay of canonical wnt signaling was performed. the assays revealed that mir-155-3p increased β-catenin-mediated transcriptional activation. overall,our data clarified that mir-155-3p mediated tnf-α-inhibited cementoblast differentiation by targeting kctd1,at least partially through canonical wnt signaling pathway. these findings reveal the expanded function of mirnas in cementoblast differentiation and mineralization. © international & american associations for dental research.