| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2093215 | Stem Cell Reports | 2016 | 13 Pages |
•MiR-34a promotes osteogenesis of hASCs in vitro and in vivo•MiR-34a directly binds to the 3′ UTR of RBP2 mRNA in hASCs•MiR-34a promotes osteogenesis of hASCs via the RBP2/NOTCH1/CYCLIN D1 network
SummaryMiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3′ UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration.
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