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

Abstract

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.

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

“…5C, 5D). These findings are consistent with previous reports that TNF-α is a proinflammatory factor that inhibits cellular cementoblastic differentiation [28,63]. However, other cyto-/chemokines, such as IL-6, Eotaxin, GM-CSF and IFN-γ, were not found to exert significant influences on the expression of CEMP-1 (Supporting Information Fig.…”

“…6A, 6B), suggesting that the contribution of the JNK pathway to M2 Mφ-enhanced cementoblastic differentiation may be mediated by other signals, such as exosomes [67,68]. There is evidence that the AKT signaling pathway plays a key role in the production of VEGF and IL-10 [69][70][71], and other cytokines, such as IFN-γ and TNF-α, can also regulate this process by activating the AKT or JNK signaling pathway [62][63][64][65][66][67][68][69][70][71][72][73], suggesting that the cytokine-cytokine and cytokine-pathway interactions are bidirectional and very complex. Although further research is necessary before the signals involved in M2-enhanced cementoblastic differentiation can be clarified, the data obtained in the present study suggest that modulation of Mφs in an in vivo milieu to positively influence PDLSCs can be useful for true periodontal regeneration.…”

IL‑1β promotes osteogenic differentiation of mouse bone marrow mesenchymal stem cells via the BMP/Smad pathway within a certain concentration range

“…Unlike IL-1β, other inflammatory factors such as TNF-α do not cause similar osteogenic promoting effects (36)(37)(38)(39). Previous findings have shown that TNF-α significantly inhibits osteogenic differentiation potential of MSCs at different concentrations (36)(37)(38)(39). In the present study, when IL-1β concentration was increased to 10 ng/ml, osteogenic promotion disappeared and osteogenic genes were downregulated.…”

“…The present results suggested that the addition of IL-1β at 0.01-1 ng/ml under osteogenic induction significantly enhanced the osteogenic differentiation of MBMMSCs, and this was demonstrated by the mRNA expression levels of downstream osteogenic genes. Unlike IL-1β, other inflammatory factors such as TNF-α do not cause similar osteogenic promoting effects (36)(37)(38)(39). Previous findings have shown that TNF-α significantly inhibits osteogenic differentiation potential of MSCs at different concentrations (36)(37)(38)(39).…”

MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in cementoblasts

“…In the previous study of our lab, tumor necrosis factor‐α (TNF‐α) has an effect on cementoblast differentiation and apoptosis (Y. L. Wang et al, ). Then, the mechanisms underlying the effect of TNF‐α on cementoblast showed that microRNA‐155‐3p regulates TNF‐α‐inhibited cementoblast differentiation (X. Wang et al, ). However, the relevance of miRNA to the inflammatory response in cementoblasts remains unknown.…”