Interleukin-15 Regulates Osteogenic/Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Under Oxidative Stress by Regulating PI3K/Akt/mTOR Signaling Pathway

Abstract

The oxidative stress process can affect bone marrow mesenchymal stem cells (BMSCs) differentiation. Interleukin (IL-15) regulates fat differentiation of BMSCs. However, the role of IL-15 in osteogenic/adipogenic differentiation of BMSCs under oxidative stress remains unclear. Rat BMSCs were cultured and randomly divided into control group; oxidative stress group and IL-15 treatment group followed by analysis of IL-15 secretion by ELISA, expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA as well as FABP4 and PPARγ 2 by Real time PCR, ALP activity, ROS content and SOD activity, and expression of PI3K/Akt/mTOR signaling proteins by Western blot. In oxidative stress group, IL-15 secretion was significantly decreased, osteocalcin, type I collagen, RUNX2 and OPN mRNA expression was reduced, along with deceased ALP activity and SOD activity, increased ROS content and FABP4 and PPARγ 2 protein expression as well as decreased expression of p-AKT and mTOR in comparison of control (P < 0 05). IL-15 treatment on oxidative stress BMSCs significantly increased IL-15 secretion and the expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA, along with increased ALP activity and SOD activity, decreased FABP4 and PPAR 2 protein expression and ROS content as well as increased expression of p-AKT and mTOR (P < 0 05). IL-15 secretion was reduced in BMSCs under oxidative stress. Promoting IL-15 secretion can improve redox balance through PI3K/Akt/mTOR signaling pathway, promote osteogenic differentiation of BMSCs.