MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture: An animal study

Bone & Joint Research

article

C. Wang¹  G-F. Zheng²  X-F. Xu³ 

[1] MRI Department, Huadong Hospital Affiliated to Fudan University;Department of Orthopedics, The Yuhang Hospital Affiliated to Medical College of Hangzhou Normal University;Department of Clinical Laboratory, Fudan University Shanghai Cancer Center;Department of Oncology, Shanghai Medical College of Fudan University

关键词: MicroRNA-186;    SMAD family member 6;    Fracture healing;    BMP signalling pathway;    Femoral fracture;   

DOI  :  10.1302/2046-3758.811.BJR-2018-0251.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

ObjectivesMicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.MethodsMicroarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.ResultsMicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing.ConclusionIn conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture.

【 授权许可】

CC BY-NC