MicroRnA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting sMAD6 in a mouse model of femoral fracture

Abstract

Objectives MicroRnAs (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. Methods Microarray 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. Results MicroRnA-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. Conclusion In 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.