Abstract
Background: e mechanism of intervertebral disc degeneration is unclear, inflammation may play an important role in it. Sphingosine 1-phosphate (S1P) is an important lipid mediator, has been confirmed to be implicated in many inflammation processes.Purpose to study the expression and role of S1PRs in the intervertebal disc (IVD) degeneration to enhance understanding of disc degeneration. Methods Degenerated and normal IVD were harvested from patients with IVD degeneration via surgery operation. The degenerated grade of each IVD specimen was assessed by Histological method. Expression of S1P receptor subtypes in each specimen was evaluated using real-time PCR, immunohistochemistry, and western blotting. The effect of S1PR on inflammation induced by interleukin-1β in nucleus pulposus (NP) cells was also assessed by real time PCR and western blot. Results The nucleus pulposus mainly expressed theS1PR1/2/3, and the expression decreased in the severe degenerated nucleus pulposus cells. The ligand, S1P, inhibited the up-regulation of matrix metallopeptidase-3(MMP-3) and ADAM metallopeptidase with thrombospondin type 1 motif 4(ADAMTS4) induced by IL-1β. Conclusions The results show that an the expression of S1PRs in degenerative discs is down-regulated as degeneration, and S1P can inhibit the inflammation response induced by IL-1β in NP cells, implicating that S1P/S1PR may contribute to IVD degeneration.
Highlights
[1] Numerous studies have shown that intervertebral (IVD) degeneration is one of the major underlying factors in chronic low back pain (LBP) [2, 3].Various changes occur with the degeneration, such as fissures in the annulus fibrosus, and dehydration in the nucleus pulposus (NP)
In order to evaluate the grade of degeneration in NP cells, Histological grading was proceeded by HE and Saf-O staining
According to the grading system [15], which generates a score between 0 and 12, we define that a grade of 0 to 4 represents a histologically normal (N), grades of 5 to 8 indicate mild degeneration (MD), and grades 9 to 12 severe degeneration (SD). all of the samples were divided into three groups, the N group includes 5 samples, the MD group includes 12 samples, and the SD group 22 samples
Summary
Chronic low back pain (LBP) is a widespread problem all over the world, which affects about 50 to 80% of adults during their lifetime. [1] Numerous studies have shown that intervertebral (IVD) degeneration is one of the major underlying factors in chronic LBP [2, 3].Various changes occur with the degeneration, such as fissures in the annulus fibrosus, and dehydration in the nucleus pulposus (NP). [1] Numerous studies have shown that intervertebral (IVD) degeneration is one of the major underlying factors in chronic LBP [2, 3].Various changes occur with the degeneration, such as fissures in the annulus fibrosus, and dehydration in the nucleus pulposus (NP). Previous studies have demonstrated that IL-1β and TNF-α are overexpressed in degenerated IVD, and led to matrix degradation in degenerated disc [8, 9]. inhibition of the effect of these cytokines may be a target for therapeutic intervention. In the light of similar biological property of nucleus pulposus cells, S1P and its receptors reflect a certain application prospect in the treatment and control of intervertebral degeneration. To the extent of our knowledge, the expression of S1P receptors or the effect of S1P in IVD degeneration have not been explored
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