Overexpressed RAD51 promoted osteogenic differentiation by activating IGF1R/PI3K/AKT pathway in osteoblasts

Background: Osteoporosis (OP) is a skeleton disease in-duced by imbalance between osteoblast and osteoclast. Osteogenic differentiation of osteoblasts is of great im-portance, and the regulatory mechanisms are urgent to be studied. Methods: Differentially expressed genes were screened from microarray profile related to OP patients. The dexamethasone (Dex) was used to induce osteogenic differentiation of MC3T3-E1 cells. MC3T3-E1 cells were exposed to microgravity environment to mimic OP model cells. Alizarin Red staining and alkaline phosphatase (ALP) staining were used to evaluate the role of RAD51 in osteogenic differentiation of OP model cells. Furthermore, qRT-PCR and western blot were ap-plied to determine expression levels of genes and pro-teins. Results: RAD51 expression was suppressed in OP patients and model cells. Alizarin Red staining and ALP staining intensity, the expression of osteogenesis-relat-ed proteins including runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen type I alpha1 (COL1A1) were increased by over-expressed RAD51. Fur-thermore, RAD51 related genes were enriched in IGF1 pathway, and up-regulated RAD51 activated IGF1 path-way. The effects of oe-RAD51 on osteogenic differen-tiation and IGF1 pathway were attenuated by IGF1R in-hibitor BMS754807. Conclusions: Overexpressed RAD51 promoted osteogenic differentiation by activating IGF1R/ PI3K/AKT signaling pathway in OP. RAD51 could be a po-tential therapeutic marker for OP.