Influence of simvastatin on the biological behavior of nucleus pulposus-derived mesenchymal stem cells

Objective(s): This research is to study the influences of different concentrations of simvastatin on the biological activities of nucleus pulposus-derived mesenchymal stem cells (NPMSC). Materials and Methods: NPMSC were cultured with different concentrations of simvastatin (0, 0.01, 0.1, and 1 mu M) and assessed to determine the possible effects of simvastatin. The cell proliferation was assessed with CCK-8 assay. The flowcytometry and multilineage differentiation were also performed to identify the stem characterization of the cells. The mRNA expressions of aggrecan, collagen type II, glucose transporter 1 (GLUT-1), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1 alpha) were determined by qRT-PCR. Results: The results demonstrated that the cells isolated from nucleus pulposus of healthy Sprague-Dawley (SD) rat met the criteria of MSC. NPMSC could form sunflower-like colonies and strongly expressed stem cell-related genes. In addition, NPMSC showed strong ability of chondrogenic, adipogenic and osteogenic differentiation. Simvastatin at certain range concentrations (0.01 mu M-0.1 mu M)) significantly promoted colony-forming rate and cell proliferation, and inhibited cell apoptosis. Simvastatin could promote expressions of aggrecan, collagen type II, HIF-1 alpha, VEGF and GLUT-1, while 0.1 mu mol/l concentration reached the maximum effect. Our study further demonstrated that HIF-1 alpha-intermediated signaling pathway might participate in regulating the biological activities of NPMSC. Conclusion: Proper concentration of simvastatin can promote the biological behavior of NPMSC, and HIF-1 alpha-intermediated signaling pathway might participate in the mechanism.