Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro

Abstract

Intervertebral disc degeneration is a disease identified as an inflammation response-participated pathological process. As a classical cellular feature, disc cell senescence is reported to be closely related with disc cell senescence. Resveratrol has a protective role against inflammation in some cells. However, its biological effects on disc cells remain largely unclear. The present study was aimed to study the effects of resveratrol on disc nucleus pulposus (NP) cell senescence in an inflammation environment. Isolated NP cells were cultured in cultured medium with (control group) or without (inflammation group) inflammatory cytokine TNF-α and IL-1β for 14 days. Resveratrol was added along with the NP cells treated with inflammatory cytokines to investigate its effects. NP cell senescence was analyzed by senescence-associated β-Galactosidase (SA-β-Gal) staining, cell proliferation, G0/1 cell cycle arrest, telomerase activity, gene/protein expression of senescence markers (p16 and p53) and NP matrix biosynthesis. In addition, the intracellular reactive oxygen species (ROS) was also analyzed. Compared with the control group, inflammation group significantly increased SA-β-Gal activity and ROS content, decreased cell proliferation and telomerase activity, promoted G0/1 cell cycle arrest, up-regulated gene/protein expression of senescence markers (p16 and p53) and matrix catabolism enzymes (MMP-3, MMP-13 and ADAMTS-4), and down-regulated gene/protein expression of NP matrix macromolecules (aggrecan and collagen II). However, resveratrol partly reversed the effects of inflammatory cytokine on these cell senescence-associated parameters. Together, resveratrol was effective to suppress cell senescence in an inflammatory environment. The present study shows new knowledge on how to retard inflammation response-initiated disc degeneration.

Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment

“…To investigate the accurate role of inflammation in mediating disc degenerative changes, many researchers carried out studies in this field. Specifically, several studies have demonstrated that interleukin-1β increases NP cell apoptosis ratio or sensitizes NP cell to certain pathological factors-mediated cellular apoptosis [20,[28][29][30][31][32][33][34]. Similarly, there are evidence that TNF-α is also an inductive factor to cause unwanted NP cell apoptosis [24,35].…”

Resveratrol Protects Human Nucleus Pulposus Cells from Degeneration by Blocking IL-6/JAK/STAT3 Pathway

“…So, in terms of RSV, there is no need to doubt its therapeutic impact on IDD because there have been plenty of studies demonstrating that in the past. However, nearly all of them have described the mechanism from the view of inhibiting the downstream pathways that have already been activated by IL-1β or TNF-α (8,9,16). We de nitely do not deny that, but we want to explain the therapeutic mechanism from a novel angle, which is IL-6 and the JAK/STAT3 pathway, the reason why we have concentrated on them and established meaningful ndings.…”

“…The anti-in ammatory, anti-cancer, anti-aging, and chondrocyteprotective effects of RSV have been demonstrated previously by many studies (10)(11)(12)(13). Recently, various researchers have shown that RSV can attenuate the deleterious effects on the intervertebral disc caused by external pathological factors, such as high glucose, IL-1β, and TNF-α (9,(14)(15)(16). It has been demonstrated that RSV can effectively mitigate cell senescence and apoptosis, and can even alleviate the in ammation response caused by the aforementioned factors by regulating different signaling pathways, such as the PI3K/AKT, extracellular regulated protein kinases 1/2 (ERK1/2), and reactive oxygen species/nuclear factor kappa beta (ROS/NF-κB) pathways (8,14,17,18), thus impeding IDD.…”

Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions

“… 164 In vitro, resveratrol partially counteracted the inflammatory effects of TNF-α and IL-1β, including decreased ECM content and increased NP cell senescence and matrix degradation enzymes (MMP-3, MMP-13, and ADAMTS-4). 165 Resveratrol also showed a similar anticatabolic effect to reverse the matrix degradation and apoptotic induction of oxidative damage caused by hydrogen peroxide in NP cells. 166 The effect may be mediated by the activation of autophagy 165 through the PI3K/Akt pathway 167 or AMPK/SIRT1 signaling pathway 168 but does not seem to involve the MAP kinase pathways or the NF-κB/SIRT1 pathway.…”