Visfatin promotes intervertebral disc degeneration by inducing IL-6 expression through the ERK/JNK/p38 signalling pathways

Abstract

Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation.

Herbal Formula Modified Bu-Shen-Huo-Xue Decoction Attenuates Intervertebral Disc Degeneration via Regulating Inflammation and Oxidative Stress

“…These core target proteins are involved in multiple signaling pathways such as inflammation, immunity, metabolism, and proliferation-related signaling pathways. Studies have confirmed that the process of IDD can be delayed by inhibiting the TNF- α -induced inflammatory response and reducing the expression of inflammatory cytokines, including IL-6 [ 44 , 45 ]. It is worth noting that TP53 was found to be potentially involved in the progression of IDD by analyzing the microarray datasets of GSE19943, GSE15227, and GSE34095 [ 46 ].…”

The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

“…The 2 −ΔΔCt (Ct: cycle threshold) was used to analyze the mRNA level, see Table 1 for primer sequence. 19 , 20 …”

“…The 2 ÀΔΔCt (Ct: cycle threshold) was used to analyze the mRNA level, see Table 1 for primer sequence. 19,20 Hydroxyproline Detection HYP was detected in lung homogenate samples using HYP kit (Nanjing Jiancheng Bioengineering Institute). Samples were weighed and pH adjusted according to the manufacturer's instructions.…”

Advances in research on fat infiltration and lumbar intervertebral disc degeneration

“…In contrast, the knockdown of visfatin expression or the use of inhibitors showed a decrease in cellular autophagy and a downregulation of autophagy-related protein expression ( 100 ). Similarly, a study modeled in rats to simulate severe IVDD and performed pathway analysis indicated that inhibition of visfatin protected the nucleus pulposus from degeneration and that focusing on epidural lipids and visfatin would be a potential therapeutic target to control the inflammation associated with IVDD ( 101 ).…”