BMP9-induced osteogenic differentiation is partially inhibited by miR-30a in the mesenchymal stem cell line C3H10T1/2
Journal of Molecular Histology(2015)
摘要
In the bone morphogenetic protein (BMP) family, BMP9 is the strongest inducer of osteogenic differentiation in mesenchymal stem cells. Recent studies have suggested that the miR-30 family regulates cell proliferation and osteoblastic differentiation. In the present study, we found that expression of only one miR-30 family member, miR-30a, first decreased and then increased during BMP9-induced osteogenic differentiation. Cell proliferation assays revealed that miR-30a had no effect on the proliferation of C3H10T1/2 cells. However, over-expression of miR-30a led to expression of an early osteogenic marker and a reduction in Runx2 expression. In addition, we observed decreases in the expression of late osteogenic markers and osteopontin, as well as calcium deposition. Dual-luciferase reporter assays indicated that this process might be mediated by suppressing Runx2 protein expression. In vivo stem cell implantation revealed inhibition of BMP9-induced ectopic bone formation and matrix mineralization by miR-30a. This study provides a better understanding of the molecular mechanisms through which miR-30a negatively regulates BMP9-induced osteogenic differentiation.
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关键词
Bone morphogenetic protein 9, MiR-30a, Runx2, Osteogenic differentiation, Mesenchymal stem cells
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