MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3

被引:98
作者
Hao, Cheng [1 ]
Yang, Shuhua [1 ]
Xu, Weihua [1 ]
Shen, Jacson K. [2 ,3 ]
Ye, Shunan [1 ]
Liu, Xianzhe [1 ]
Dong, Zhe [1 ]
Xiao, Baojun [1 ]
Feng, Yong [1 ,2 ,3 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Orthoped Hosp, Wuhan 430074, Hubei, Peoples R China
[2] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
MESENCHYMAL STEM-CELLS; TGF-BETA; OSTEOBLAST DIFFERENTIATION; NONTRAUMATIC OSTEONECROSIS; GENE-EXPRESSION; STROMAL CELLS; BONE; DEXAMETHASONE; RUNX2; PROLIFERATION;
D O I
10.1038/srep22599
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Steroid-induced osteonecrosis of femoral head (ONFH) is a serious complication of glucocorticoid (GC) use. We investigated the differential expression of miRs in the mesenchymal stem cells (MSCs) of patients with ONFH, and aimed to explain the relationship between GC use and the development of MSC dysfunction in ONFH. Cells were collected from bone marrow of patients with ONFH. Samples were assigned to either GCs Group or Control Group at 1:1 matched with control. We then used miRNA microarray analysis and real-time PCR to identify the differentially expressed miRs. We also induced normal MSCs with GCs to verify the differential expression above. Subsequently, we selected some of the miRs for further studies, including miRNA target and pathway prediction, and functional analysis. We discovered that miR-708 was upregulated in ONFH patients and GC-treated MSCs. SMAD3 was identified as a direct target gene of miR-708, and functional analysis demonstrated that miR-708 could markedly suppress osteogenic differentiation and adipogenesis differentiation of MSCs. Inhibition of miR-708 rescued the suppressive effect of GC on osteonecrosis. Therefore, we determined that GC use resulted in overexpression of miR-708 in MSCs, and thus, targeting miR-708 may serve as a novel therapeutic biomarker for the prevention and treatment of ONFH.
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页数:13
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