Bone Morphogenetic Protein Receptor Type II Promotes Odontogenic Differentiation of Human Dental Pulp Stem Cells Via...

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

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.

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.

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.