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

  • Minli Qiu Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Ya Xie Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Liudan Tu Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Minjing Zhao Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Mingcan Yang Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Linkai Fang Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China
  • Jieruo Gu Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Tianhe District, Guangzhou, 510630, China

Abstract

Background: Osteoporosis (OP) is a skeleton disease induced by imbalance between osteoblast and osteoclast. Osteogenic differentiation of osteoblasts is of great importance, 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 applied to determine expression levels of genes and proteins. Results: RAD51 expression was suppressed in OP patients and model cells. Alizarin Red staining and ALP staining intensity, the expression of osteogenesis-related proteins including runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen type I alpha1 (COL1A1) were increased by over-expressed RAD51. Furthermore, RAD51 related genes were enriched in IGF1 pathway, and up-regulated RAD51 activated IGF1 pathway. The effects of oe-RAD51 on osteogenic differentiation and IGF1 pathway were attenuated by IGF1R inhibitor BMS754807. Conclusions: Overexpressed RAD51 promoted osteogenic differentiation by activating IGF1R/PI3K/AKT signaling pathway in OP. RAD51 could be a potential therapeutic marker for OP.

Published
2023-02-16
Section
Articles