Isofraxidin attenuates IL-1ß-induced inflammatory response in human nucleus pulposus cells.

Inflammation has been demonstrated to be the key factor for intervertebral disc degeneration (IVD), which remains a major public health problem. Isofraxidin is a coumarin compound that possesses strong anti-inflammatory activity. However, the role of isofraxidin in IVD remains unclear. The aim of this study was to evaluate the effects of isofraxidin on inflammatory response in human nucleus pulposus cells (NPCs) exposed to interleukin-1ß (IL-1ß). The results proved that isofraxidin attenuated the IL-1ß-induced significant increases in inflammatory mediators and cytokines including nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and IL-6. Besides, isofraxidin also inhibited the induction effect of IL-1ß on matrix metalloproteinases (MMP)-3 and MMP-13. Moreover, the NF-κB activation caused by IL-1ß was significantly inhibited by isofraxidin treatment. These findings suggested that isofraxidin alleviates IL-1ß-induced inflammation in NPCs. Our work provided an idea that isofraxidin might act as a novel preventive role in IVD.

MicroRNA-30c abrogation protects against spinal cord ischemia reperfusion injury through modulating SIRT1.

Spinal cord ischemia/reperfusion (I/R) injury is a severe complication in many surgeries. Although microRNAs (miRNAs) are involved in I/R-caused spinal cord injury (SCI), the mechanism that underlies miR-30c interacted with SCI remains elusive. In this study, I/R surgery or oxygen-glucose deprivation (OGD) were performed to establish SCI model in vivo or in vitro, respectively. Basso, Beattie and Bresnahan (BBB) score, spinal cord infarct, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, flow cytometry and enzyme linked immunosorbent assays (ELISA) were used to investigate SCI. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the abundances of miR-30c and sirtuin 1 (SIRT1) either in spinal cord or PC12 cells. Luciferase assay and RNA immunoprecipitation (RIP) were performed to probe the interaction between miR-30c and SIRT1. Western blot and immunofluorescence assays were used to analyze SIRT1 protein expression. Our results showed that I/R increased miR-30c expression and induced SCI, revealed by decreasing BBB score, enhancing apoptosis, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression. However, miR-30c knockdown attenuated I/R-induced SCI in vivo. Moreover, depletion of miR-30c protected PC12 cells against OGD-caused apoptosis and inflammatory response. In addition, SIRT1 was limited by miR-30c, silencing of which reversed anti-miR-30c-mediated inhibitory effect on apoptosis and secretion of inflammatory cytokines in PC12 cells after OGD treatment. Collectively, abrogation of miR-30c inhibited spinal cord ischemia reperfusion injury through targeting SIRT1, providing a promising biomarker of prognosis and therapeutic for SCI.