Expression and Role of Sphingosine 1-Phosphate Receptors in Intervertebral Disc Degeneration

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