Bone Morphogenetic Protein Receptor Type II Promotes Odontogenic Differentiation of Human Dental Pulp Stem Cells Via Runt-related Transcription Factor 2.

Abstract

Objective: To investigate the molecular mechanism by which bone morphogenetic protein receptor type 2 (BMPR2) regulates the odontogenic differentiation of dental pulp stem cells.

Methods: Human dental pulp stem cells (hDPSCs) with lentiviral vector-mediated BMPR2 overexpression and knockdown were generated. Cell proliferation was assessed using a cell counting kit-8 assay. The odontogenic differentiation potential of hDPSCs was examined using alkaline phosphatase and alizarin red S staining. The expression of odontogenic differentiation markers and critical mediators of bone morphogenetic protein (BMP)-suppressor of mothers against decapentaplegic (SMAD) signalling was analysed using real-time quantitative polymerase chain reaction and western blotting.

Results: BMPR2 overexpression promoted odontogenic differentiation of hDPSCs but suppressed their proliferation, which was contrary to the findings in the BMPR2 knockdown group. Moreover, BMPR2 overexpression activated the BMP-SMAD-Runt-related transcription factor 2 (RUNX2) signalling cascade. RUNX2 overexpression partially recaptured the effects of BMPR2 knockdown on odontogenic differentiation of hDPSCs.

Conclusion: These results indicate that BMPR2 promotes odontogenic differentiation of hDPSCs by activating BMPR2-SMAD1/5/8-RUNX2 signalling, and that targeting this cascade could be a promising strategy for gene therapy in human tooth development.