IGF-1 induced intervertebral disc annulus fibrosus cell aging through the inhibition of SIRT1 activity

English Keywords:Annulus fibrosus cells  IGF-1  SIRT1  Intervertebral disc aging

English Abstract:

  【Abstract】 Objectives: To investigate the mechanism of insulin-like growth factor 1(IGF-1) in mediating intervertebral disc cell aging through regulating the activity of the silent information regulator sirtuin 1(SIRT1). Methods: The intervertebral disc tissues of eight-week old female Spargue Dawley(SD) rats were dissected, from which annulus fibrosus(AF) cells were isolated and cultured in vitro. The effects of IGF-1 on the aging of AF cells were studied by β-galactosidase(SA-β-Gal) staining, cell proliferation assays, and cell migration experiments, in exposure to different concentrations of recombinant rat IGF-1(0, 1, 10, 50, 100ng/mL) in culture. The molecular mechanism of IGF-1 on AF cells was further explored by Western blot analysis. Results: After treatment with exogenous IGF-1 at different concentrations, SA-β-Gal staining and western blot results showed that IGF-1 promoted AF cell aging in a concentration-dependent manner. The CCK-8 analysis showed that low concentrations of IGF-1 significantly induced AF cell proliferation. Transwell assay results showed that low concentrations of IGF-1 profoundly enhanced the migratory capability of AF cells, whereas IGF-1 at high concentrations demonstrated no significant effect on AF cell migration. Western blot results showed that IGF-1 could downregulate the expression of SIRT1 and elevate the acetylation of p53. Conclusions: IGF-1 can promote AF cell aging though inhibiting SIRT1 expression and activity.