Resveratrol protects human nucleus pulposus cells from degeneration by blocking IL-6/JAK/STAT3 pathway

Cenhao Wu,Hao Yu,Ming Yang,Jun Zou,Yingjie Wang,Qi Yan,Jun Ge,Huilin Yang

doi:10.1186/s40001-021-00555-1

Abstract

BackgroundNucleus pulposus cells’ (NPCs’) degeneration is mainly responsible for the intervertebral disc degeneration (IDD), which is closely related to inflammatory response. Among the major proinflammatory factors that are related to NPCs’ degeneration, interleukin-6 (IL-6) and its downstream JAK/STAT3 pathway have received recent attention. The goal of our study is to figure out whether or how resveratrol (RSV) can protect NPCs from degeneration by affecting IL6/JAK/STAT3 pathway.MethodsDifferent concentrations of RSV were added to NPCs’ mediums. Cell viability was measured by MTT assay and crystal violet staining. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression level was determined by western blot. mRNA expression level was measured by qPCR.ResultsOur study showed that RSV improved NPCs’ cell viability. It also inhibited cell apoptosis and cell cycle arrest, which were accompanied by the increased expression level of heat shock protein 90 (HSP90) and N-Cadherin. What’ more, RSV also improved the NPCs’ degeneration which was reflected in the increase of extracellular matrix (collagen II, Aggrecan). Moreover, RSV significantly attenuated the level of IL-6 secretion, which was accompanied by less phosphorylation of the transcription factors Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3).ConclusionRSV exerted its protective effect on HNPCs’ degeneration by improving cell survival and function. The possible mechanism may be associated with the suppression of JAK/STAT3 phosphorylation and the decreased IL-6 production, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK/STAT3 pathway.

Highlights

Nucleus pulposus cells’ (NPCs’) degeneration is mainly responsible for the intervertebral disc degeneration (IDD), which is closely related to inflammatory response
What is more is that the related downstream pathways, such as AMP-activated protein kinase/Sirtuin1 (AMPK/SIRT1), phosphatidylinositol-3-kinases/protein kinase B (PI3K/ AKT), and Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and the various therapies that target them for prevention IDD have become a hot research topic in recent times [6,7,8,9]
It has been demonstrated that RSV can effectively mitigate cell senescence and apoptosis, and can even alleviate the inflammation 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], impeding IDD

Summary

Introduction

Nucleus pulposus cells’ (NPCs’) degeneration is mainly responsible for the intervertebral disc degeneration (IDD), which is closely related to inflammatory response. Among the major proinflammatory factors that are related to NPCs’ degeneration, interleukin-6 (IL-6) and its downstream JAK/STAT3 pathway have received recent attention. The goal of our study is to figure out whether or how resveratrol (RSV) can protect NPCs from degeneration by affecting IL6/JAK/STAT3 pathway. There is quite a gap—the aforementioned studies have shown a potent anti-inflammatory/anti-degenerative ability of RSV preventing IDD, though most were carried out under conditions, where nucleus pulposus cells (NPCs) were stimulated by exogenous stimulatory factors in advance, and so there are less investigations in the literature on how RSV affects NPCs at a normal physiological state. The mechanism of how exactly RSV affects NPCs is still a challenge for scientists globally These are the reasons why we conducted our study and doing so, we sought to explain these matters from the perspective of the IL6/ JAK/STAT3 pathway

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Conclusion