Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Promote Osteoporosis and Osteoblast Proliferation by Inhibiting Bax/Bcl-2/Caspase Signaling Pathway

Abstract

The current treatment for osteoporosis cannot restore the lost bone mass. Exosomes can not only delay bone loss, but also promote osteogenic proliferation and differentiation. This study aims to determine whether BMSCs-derived exosomes could improve osteoporosis in rats. A rat model of osteoporosis was established by excising bilateral ovaries. Whole bone marrow cell inoculation method and adherent purification were used to culture rat bone marrow mesenchymal stem cells (BMSCs). Osteoporosis rats were treated with BMSCs-derived exosomes followed by analysis of serum osteocalcin level by ELISA and bone mineral density and volume fraction by Micro-CT. Osteoblasts were treated with exosomes followed by analysis of cell proliferation by CCK-8 assay and expression of key molecules in the apoptotic signaling by real-time PCR and Western blot. Serum osteocalcin, bone mineral density and volume fraction in OVX group were significantly lower than those in control group and Exo group (P < 0.05) with significant differences between Exo group and CON group. With the increase of exosome concentration, the survival rate of osteoblasts was increased gradually. Cleaved Caspase-3 expression was reduced and Bcl-2 level was elevated gradually. BMSCs-derived exosomes can promote osteoblast proliferation by inhibiting apoptotic signaling pathway and improving osteoporosis.