miR-155-5p regulates mesenchymal stem cell osteogenesis and proliferation by targeting GSK3B in steroid-associated osteonecrosis

被引:11
|
作者
Wu, Fei [1 ]
Huang, Wei [2 ]
Yang, Yue [1 ]
Liu, Feng [1 ]
Chen, Jin [3 ]
Wang, Guangyong [3 ]
Sun, Zhibo [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Orthoped, Wuhan 430060, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthoped, Wuhan, Hubei, Peoples R China
[3] Yiling Hosp, Dept Orthoped, Yichang, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
GSK3B; miR-155-5p; MSCs; steroid-associated osteonecrosis; DIFFERENTIATION; CONSTRICTION; INHIBITION;
D O I
10.1002/cbin.11470
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
microRNAs (miRNAs) have recently been recognized as playing an important role in bone-associated diseases. This study investigated whether the reduced miR-155-5p in steroid-associated osteonecrosis of the femoral head (ONFH) attenuated osteogenic differentiation and cell proliferation by targeting GSK3B. Bone marrow was collected from the proximal femurs of patients with steroid-associated ONFH (n = 10) and patients with new femoral neck fracture (n = 10) and mesenchymal stem cells (MSCs) were isolated. The expression profile, the biological function of miR-155-5p, and the interaction between miR-155-5p and GSK3B were investigated by cell viability measurement, western blot, real-time polymerase chain reaction, luciferase reporter assay, and Alizarin Red S (ARS) staining of MSCs. The MSCs that were obtained from the femoral neck fracture group and from the steroid-associated ONFH group were transfected with or without miR-155-5p. We found that, in ONFH samples, the level of mature miR-155-5p was significantly lower than that of control samples. By inhibiting GSK3B, miR-155-5p promoted the nuclear translocation of beta-catenin, increased the expression of osteogenesis-related genes, and facilitated the proliferation and differentiation of MSCs. Restoring the expression of GSK3B in MSCs partially reversed the effect of miR-155-5p. These findings suggest that reduced miR-155-5p in steroid-associated ONFH attenuates osteogenic differentiation and cell proliferation by increased levels of GSK3B and inhibition of Wnt signaling.
引用
收藏
页码:83 / 91
页数:9
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