Bone Marrow Mesenchymal Stem Cell-Exosomes (BMSC-ExO) Promote Osteogenic Differentiation In Vitro and Osteogenesis In Vivo by Regulating miR-318/Runt-Related Transcription Factor 2 (RUNX2)

Abstract

Primary osteoporosis (PMOP) is characterized by bone mass reduction and bone microstructure destruction, increased bone fragility and prone to fracture, which is partially caused by ovarian dysfunction and decreased estrogen content. Bone marrow mesenchymal stem cell exosomes (BMSC-ExO) can improve PMOP. In this study, BMSC-EXO was used to study the role and function of miR-318 and Runx2 in PMOP. Human osteogenitor cells were isolated from PMOP patients with primary osteoporosis. After BMSC-exo treatment, miR-318 and Runx 2 level was tested by RT-qPCR and Western blot. In addition, mice in OVX group were treated with BMSC-ExO (bilateral ovaries were removed) to observe the effect of BMSC-ExO on bone tissue. Our results showed that BMSC-exo treatment significantly decreased miR-318 level, upregulated RUNX2 expression and increased ALP activity. In addition, BMSC-exo administration ameliorated the declined bone mass and bone formation in osteoporotic femurs in OVX mice. In conclusion, BMSC-Exo enhances Runx2 levels by down-regulation of miR-318, thereby promoting osteogenic differentiation of osteogenitor cells, providing new potential therapeutic targets for treating PMOP.