Chemerin/ChemR23 regulates cementoblast function and tooth resorption in mice via inflammatory factors

Abstract Background Periodontitis and orthodontic treatment can lead to inflammatory root resorption (IRR) through an unclear mechanism. Chemerin, a novel chemoattractant protein, is closely associated with inflammation, affects osteoblast and osteoclast differentiation, and may play a role in IRR. We aimed to explore possible roles of the chemerin/ChemR23 interaction in cementoblast function and IRR and reveal a new IRR therapeutic target. Methods Cementoblast function‐related gene and protein expression in the immortalized murine cementoblast cell line OCCM‐30 after treatment with chemerin and siChemR23 was examined by qRT‐PCR and Western blotting. The roles of the MAPK and PI3K‐Akt signaling pathways were studied using specific inhibitors. Cementoblast cytokine production under different treatment conditions was measured by enzyme‐linked immunosorbent assay and qRT‐PCR. Additionally, we modeled IRR in wild‐type and chemerin‐overexpressing mice and injected transgenic mice with anti‐ChemR23 antibody to block ChemR23. We then calculated the root resorption volume and examined periodontal tissue cathepsin K, Runx2, tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) expression. Result Chemerin suppressed cementoblast differentiation and mineralization and exerted a proinflammatory effect on cementoblasts. These effects were partially reversed by siChemR23 and reversed to different extents by p38, Erk1/2 and PI3K‐Akt pathway inhibition, suggesting p38, Erk1/2 and PI3K‐Akt pathways as signaling pathways downstream of chemerin/ChemR23. In vivo, chemerin overexpression worsened IRR. Moreover, chemerin expression was positively correlated with TNF‐α, IL‐6, and cathepsin K expression and negatively correlated with Runx2 expression. ChemR23 downregulation reversed these effects. Conclusion Chemerin/ChemR23 induced TNF‐α and IL‐6 expression dependent on Erk1/2, p38 MAPK, and PI3K‐Akt signaling pathway activation, thereby regulating cementoblast function and affecting IRR.