miR-384-5p Targets Gli2 and Negatively Regulates Age-Related Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells

被引:29
|
作者
Li, Xiaoming [1 ]
Wu, Jinhui [2 ]
Liu, Shu [1 ]
Zhang, Ke [2 ]
Miao, Xiong [1 ]
Li, Jingfeng [1 ]
Shi, Zhicai [1 ]
Gao, Yang [3 ]
机构
[1] Naval Med Univ, Dept Orthoped, Changhai Hosp, 168 Changhai Rd, Shanghai 200433, Peoples R China
[2] Naval Med Univ, Dept Orthoped, Changzheng Hosp, Shanghai, Peoples R China
[3] Chinese PLA Peoples Liberat Army Gen Hosp, Dept Orthoped, Beijing, Peoples R China
关键词
aging; bone marrow stem cells; miR-384-5p; Gli2; osteogenic differentiation; MACROPHAGE AUTOPHAGY; OSTEOBLAST; PROLIFERATION; MECHANISM; RESCUES;
D O I
10.1089/scd.2019.0044
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:791 / 798
页数:8
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