Effect of SRY-Associated High Mobility Group Box 9 (SOX9) on Bone Formation of Bone Marrow Mesenchyma Stem Cells in High Glucose Environment by Regulating ERKP38 Signaling Pathway

摘要

Differentiation of BMSCs into osteoblasts is beneficial for the prevention and treatment of osteoporosis. SRY-associated high mobility group box 9 (SOX9) in involves in mammalian development and progression of various diseases, but the role of SOX9 in bone formation of BMSCs in high glucose environments remains unclear. Rat BMSCs were isolated and randomly assigned into control group, high glucose group and SOX9 siRNA group followed by analysis of SOX9 level by real time PCR and Western blot, cell proliferation and Caspase 3 activity, ALP activity and Runx2 expression, TNF-alpha and IL-2 secretion by ELISA, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, expression of ERK/P38 signaling protein by Western blot. SOX9 expression in high glucose group was significantly increased along with significantly inhibited cell proliferation, increased Caspase 3 activity, TNF-alpha and IL-2 secretion, decreased ALP activity, increased MPO content, decreased SOD activity, Runx2 and ERK/P38 protein phosphorylation (P < 0.05). Transfection of SOX9 siRNA significantly reduced SOX9 expression in high glucose group, significantly promoted cell proliferation, decreased Caspase 3 activity, TNF-alpha and IL-2 secretion, enhanced ALP activity, decreased MPO, increased SOD, Runx2 and ERK/P38 phosphorylation (P < 0.05). SOX9 expression is increased in high glucose environment. Down-regulation of SOX9 can inhibit the apoptosis of BMSCs, inhibit oxidative stress and inflammation, promote proliferation and osteogenic differentiation in high glucose environment by regulating ERK/P38 signaling pathway.