PPAR-γ agonist pioglitazone protects against IL-17 induced intervertebral disc inflammation and degeneration via suppression of NF-κB signaling pathway

Abstract Interleukin-17 (IL-17) is the production of T helper type 17 (Th17) cells and has been reported to play a pro-inflammatory role in the immunopathogenesis of intervertebral disc degeneration. Peroxisome proliferator-activated receptor γ (PPAR-γ) activators display anti-inflammatory and anti-degeneration roles in osteoarthritis and rheumatoid arthritis. However, the expression level of PPAR-γ and related regulatory mechanisms in the nucleus pulposus tissues are not clear. Herein we report that PPAR-γ was down-regulated both in the nucleus pulposus tissue of intervertebral disc degeneration patient and in the cultured nucleus pulposus cells stimulated with IL-17. This study was undertaken to investigate the potential therapeutic effect of pioglitazone, as a PPAR-γ ligand, and its underlying molecular mechanism in IL-17-induced human intervertebral disc degeneration model in vitro . Our results indicate that pioglitazone administration suppressed the production of pro-inflammatory cytokines and down-regulated the mRNA expression levels of inflammatory mediators in the cultured human nucleus pulposus cells and tissue. Consistently, pioglitazone decreased the levels of metalloproteinase and maintained the expression of critical matrix components, such as aggrecan and type II collagen. Moreover, the activation of NF-κB signaling in the nucleus pulposus tissue during the intervertebral disc degeneration development was antagonized by pioglitazone administration. In conclusion, our current findings provide scientific evidence for the assessment of pioglitazone as a potential therapeutic approach to treat the intervertebral disc degeneration.