Tumor Necrosis Factor-α Inhibits Differentiation of Bone Marrow Mesenchymal Stem Cells into Osteoblasts by Inhibiting Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Pathway

Abstract

Bone marrow mesenchymal stem cells (BMSCs) have the potential for multi-directional differentiation. Tumor necrosis factor-α (TNF-α) plays a role in many diseases. However, the role of TNF-α in the differentiation of BMSCs into osteoblasts remains unclear. Rat-derived BMSCs were divided into normal control group and TNF-α group (5 ng/ml or 10 ng/ml) followed by analysis of BMSCs proliferation by MTT, Caspase3 activity, TNF-α mRNA and serum secretion by Real time PCR and ELISA, ALP activity, Runx2, OP and OC level by Real time PCR and PI3K/AKT signaling protein expression by Western blot. TNF-α significantly promoted the expression of TNF-α mRNA and serum secretion, inhibited cell proliferation, increased Caspase3 and ALP activity, decreased Runx2 and OP expression, and inhibited AKT phosphorylation compared to control (P < 0.05). The inhibition of osteogenic differentiation of BMSCs was more obvious with the increase of TNF-α concentration. TNF-α can inhibit the proliferation of BMSCs, promote apoptosis and inhibit BMSCs osteogenic differentiation via inhibiting the PI3K/AKT pathway.