Reduced miR-9 and miR-181a expression down-regulates Bim concentration and promote osteoclasts survival.

Tibial plateau fractures are often the result of blunt trauma and are associated with severe soft-tissue injury. Operative management of high-energy fractures remains difficult and challenging because the injuries often associated with serious complications. MicroRNAs (miRNAs) are the class of short noncoding single-stranded RNA molecules that negatively regulate gene expression. miRNAs contribute to every step of osteogenesis from embryonic bone development to maintenance of adult bone tissue, and disturbed miRNAs expression are identified related to osteoporosis, osteosarcoma, post-traumatic arthritis and bone remodeling. But our understandings about the roles of miRNAs in tibial plateau fractures repairing process are rare. In this study, we first detect seven candidate miRNAs expression in the SF cells of the mouse model. The results indicated that miR-9 and miR-181a were down-regulated significantly five days after injury. By using dual luciferase assay and western blot, we confirmed that the expression of Cbl is repressed by miR-9 and miR-181a. Meanwhile, the amount of ubiquitinated Bim was raised and the total Bim was reduced by miRNA inhibitors. Further functional study indicated that reduced miR-9 and miR-181a expression can active RAW264.7 cells migration ability and raise the primary mouse osteoclasts survival rate in vitro. To our understood, this is the first study about the function of disturbed miRNAs in the tibial plateau fracture mouse model, and may expand our understanding about post tibial plateau fracture recover and post-traumatic sequelae generation.