Dimethyl fumarate protects nucleus pulposus cells from inflammation and oxidative stress and delays the intervertebral disc degeneration.

Abstract

Lower back pain is a common problem in middle-aged and elderly people, and intervertebral disc degeneration (IVDD) is often the main cause. The present study aimed to explore the effects of dimethyl fumarate (DMF) on inflammation and oxidative stress in the intervertebral disc. C57/BL6 mice were used to construct an IVDD model by tail suspension and daily intraperitoneal injections of 10 mg/kg DMF were administered to analyze the effects of DMF on IVDD. In addition, human nucleus pulposus (NP) cells were cultured and stimulated cells with recombinant human IL-1β and DMF to examine the effects of DMF on inflammation and oxidative stress in NP cells. DMF significantly increased the intervertebral disc height index of mice and inhibited the degradation of the extracellular matrix of mouse NP tissue. In addition, DMF also decreased the expression of inflammatory factors [including IL-6, IL-8, matrix metalloproteinase (MMP)3 and MMP13] in NP cells. In terms of oxidative stress, DMF significantly increased the antioxidative stress response in NP cells and reduced endoplasmic reticulum stress. DMF also increased the activity of the nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1 signaling pathway in NP cells and increased the phosphorylation of Akt. DMF also increased the anti-inflammatory and antioxidative ability of NP cells by promoting the activity of the Nrf2/HO-1 and PI3K/Akt signaling pathways, thus delaying IVDD.

• Authors: Hainian Zhu, Gang Chen, Yuhua Wang, Xuchen Lin, Jingyuan Zhou, Zengshun Wang, Nanangxiu Suo
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 20 Issue 6 Pg. 269 (Dec 2020) ISSN: 1792-0981 [Print] Greece
• PMID: 33199994 (Publication Type: Journal Article)
• Copyright: Copyright: © Zhu et al.