MicroRNA-23a inhibits osteogenesis of periodontal mesenchymal stem cells by targeting bone morphogenetic protein signaling.

Abstract

OBJECTIVES\nTo investigate the role of microRNA-23a (miR-23a) in the osteogenesis of periodontal mesenchymal stem cells (PDLSCs) in periodontitis.\n\n\nMATERIALS AND METHODS\nGingival crevicular fluid samples were collected from 21 control subjects and 29 patients with chronic periodontitis. MiR-23a was determined by quantitative real-time PCR. PDLSCs were transfected with miR-23a overexpressing lentiviruses. Subsequently, PDLSCs were induced with osteogenic differentiation media. Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase activity assay, Alizarin red staining, and qRT-PCT detection of osteogenic gene expression. Western blot was performed to detect the protein levels of the SMAD family member 1/5/9 (Smad1/5/9) and their phosphorylation level. TargetScan was used to predict the target gene of miR-23a. Cotransfections of bone morphogenetic protein receptor type 1B (BMPR1B) and miR-23a applied to explore the relationship between BMPR1B and miR-23a.\n\n\nRESULTS\nMiR-23a was significantly increased in PDLSCs and gingival crevicular fluid of periodontitis patients. Patients with gingival crevicular fluid miR-23a levels above a threshold showed more clinical indicators of periodontitis. After periodontal therapy, miR-23a levels significantly decreased. Overexpression miR-23a inhibited osteogenesis of PDLSCs, which was evidenced by reduced Alizarin Red S and osteogenic gene expressions. In addition, miR-23a inhibited the phosphorylation of Smad1/5/9. TargetScan predicted that BMPR1B is a target gene of miR-23a. Overexpression of BMPR1B abolished the effects caused by overexpression of miR-23a.\n\n\nCONCLUSION\nOur study provides novel evidence that miR-23a acts as a negative regulator of osteogenesis in periodontitis patients PDLSCs and that miR-23a may serve as a biomarker and potential target of periodontitis.