Bone fracture healing is a complex physiologic process that involves changes in the expression of several thousand genes. Long noncoding RNAs (lncRNAs) may have critical biological roles in this process. The objectives of the present study were to determine whether BMSC-derived exosomal lncTUG1 can enhance osteogenic differentiation and thereby promoting bone fracture recovery and to investigate its potential mechanisms of action. Bone marrow mesenchymal stromal cells were isolated from mice and cultured for the following experiments. After adipogenic and osteogenic differentiation induction, Oil Red O, alizarin red S, and alkaline phosphatase staining solutions were applied to confirm the formation of lipid droplets and calcium nodules. Western blotting analyses, real-time reverse transcription PCR assays, luciferase reporter were performed to confirm relative RNA and protein expressions and luciferase activities of transfected cells. RNA pull-down and RNA immunoprecipitation assays were also carried to verify the interaction between lncTUG1 and miR-22-5p. Additionally, a mouse model of closed femoral fractures was generated to evaluate the in vivo effect of increased lncTUG1 on fracture healing. BMSC-derived exosomal lncTUG1 enhanced the activity of osteoblasts. Overexpression of miR-22-5p reversed the osteopromoting effect of increased lncTUG1. The knockdown of Anxa8 reversed the osteogenic effect of miR-22-5p inhibitors, indicating an interaction between Anxa8 and miR-22-5p. Upregulation of lncTUG1 could promote the fracture recovery in vivo. In conclusion, the present study highlights the functional importance of BMSC-derived exosomal lncTUG1 in the process of bone fracture recovery.
[1]Jilin Univ, China Japan Union Hosp, Dept Clin Lab, Changchun 130033, Peoples R China.
[2]Shandong First Med Univ, Shandong Prov Hosp, Dept Orthoped, 324 Jingwuweiseven Rd, Jinan 250014, Shandong, Peoples R China.
[3]Shandong First Med Univ, Shandong Acad Med Sci, 6699 Qingdao Rd, Jinan 271016, Shandong, Peoples R China.
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