SIRT1 Plays a Protective Role in Intervertebral Disc Degeneration in a Puncture-induced Rodent Model

Study Design. Experimental animal study of treatment of intervertebral disc (IVD) degeneration. Objective. This report aims to evaluate the in vivo effects of SIRT1 on IVD biology and to explore its potential mechanism. Summary of Background Data. Silent mating type information regulator 2 homolog 1 (SIRT1) has attracted immense attention because of its functions in a variety of aging-related diseases. Despite previous studies indicated that SIRT1 showed a unique expression with degeneration in some in vitro study, there is no in vivo research on the role SIRT1 plays in IVD and its mechanism. Methods. Coccygeal discs were punctured to induce disc degeneration. Sixteen C57BL/6J mice received either Carboxy methocel (Vehicle) or Resveratrol (RES) gavage. Eight SIRT1(+/-) mice and their SIRT1(+/+) littermates were also used in this study. At 2 and 6 weeks after puncture, magnetic resonance images were obtained. The mice were subsequently killed, and the spine was extracted for further evaluation. Results. Coccygeal disc puncture caused IVD degeneration in the mice. A SIRT1 activator, RES, markedly ameliorated this pathological change, as demonstrated by stronger signal intensity in the T2-weighted images, as well as a significantly lower magnetic resonance imaging grade (at 2 wk vs. Vehicle group P < 0.001). Histological analysis also revealed an improvement in the RES group compared with the Vehicle group (P < 0.05). Genetic ablation of 1 allele significantly enhanced the level of damage relative to the wild-type mice. In addition, SIRT1 activation suppressed the expression of p16 and at the same time, promoted proliferating cell nuclear antigen and type II collagen expression in disc cells, whereas genetic ablation of 1 allele SIRT1 exhibited the opposite consequence. Conclusion. The SIRT1 activator RES protects against puncture-induced disc injury whereas SIRT1 deficiency aggravates tissue injury; the protective role of SIRT1 is partly mediated by suppressing p16, which plays a role in elevating the decreased proliferative ability of the senescent nucleus pulposus cells.