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.
Highlights
Intervertebral disc degeneration (IDD)-caused pathological changes in the spine-associated tissues is a main reason for low back pain [1]
Results showed that the intracellular reactive oxygen species (ROS) content in the inflammation group was obviously higher than that in the control group, whereas resveratrol partly decreased the intracellular ROS content of nucleus pulposus (NP) cells-treated with inflammatory cytokines (Figure 1)
Our results showed that NP cells in the inflammation group had a significantly increased fraction of the G0/G1 phase and a significantly decreased fraction of the S phase compared with the control group
Summary
Intervertebral disc degeneration (IDD)-caused pathological changes in the spine-associated tissues is a main reason for low back pain [1]. Current treatments for disc degeneration-caused spinal disease, either conservative therapy or surgical treatment, mainly aimed to alleviate pain syndrome, and these treatments cannot biologically retard or regenerate disc degeneration [2,3]. It has been indicated that degenerative changes first occur in the NP region during disc degeneration [5,6]. Increasing evidence has indicated that cell senescence participates in the process of disc degeneration. Cell senescence is positively related with the degree of disc degeneration [6,9]. Inhibition of disc cell senescence may be an important point to retard disc degeneration
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