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  • Title: miR-384-5p Targets Gli2 and Negatively Regulates Age-Related Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells.
    Author: Li X, Wu J, Liu S, Zhang K, Miao X, Li J, Shi Z, Gao Y.
    Journal: Stem Cells Dev; 2019 Jun 15; 28(12):791-798. PubMed ID: 30950325.
    Abstract:
    Aberrant microRNA expression correlates with age-related osteoporosis, which impairs bone formation by regulating osteoblastic activity, thus leading to age-related bone loss. In this study, we observed that miR-384-5p was significantly upregulated in bone marrow mesenchymal stem cells (BMSCs) from aged rats compared with BMSCs from young rats. In vitro functional assays revealed that overexpression of miR-384-5p in young BMSCs inhibited osteogenic differentiation and accelerated senescence, whereas knockdown of miR-384-5p in aged BMSCs had the opposite effects. Furthermore, we demonstrated that miR-384-5p inhibited the expression of Gli2 at both the mRNA and protein levels by directly binding to the 3' untranslated region of Gli2 mRNA. The osteogenic capacity of Gli2-knockdown BMSCs was rejuvenated by miR-384-5p inhibition. Finally, in vivo assays showed that the inhibition of miR-384-5p prevented bone loss and increased the osteogenic capacity in aged rats. Overall, our study suggests that miR-384-5p functions as a negative regulator of osteogenesis, indicating that the inhibition of miR-384-5p may be a therapeutic strategy against age-related bone loss.
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