H19 and Foxc2 synergistically promotes osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.

OBJECTIVE: To investigate the mechanism of H19 on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

METHODS: Ovariectomized (OVX) mouse model was established. RNA immunoprecipitation and RNA pull-down assays were performed to determine the correlation between H19 and forkhead box C2 (Foxc2). Chromatin immunoprecipitation assay was used to identify whether Foxc2 binds to the Wnt4 promoter region. Molecules expressions were measured by quantitative real-time polymerase chain reaction and western blot.

RESULTS: We found that H19 expression was reduced in the serum of patients with postmenopausal osteoporosis and BMSCs of OVX mice, and overexpression of H19 promoted osteogenic differentiation of BMSCs. Additionally, Foxc2 could bind to the Wnt4 promoter and promote its transcription. We also showed that H19 could bind to Foxc2, and H19/Foxc2 regulated Wnt promoter expression in a synergistic fashion, and H19/Foxc2 regulated osteogenic differentiation of BMSCs through Wnt-β-catenin pathway.

CONCLUSION: H19 and Foxc2 synergistically promoted osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.