Expression and role of Sphingosine 1-phosphate receptors in intervertebral disc degeneration.

IVD degeneration is a widespread problem all over the world, which a variety of inflammatory cytokines have been implicated in, while Sphingosine 1-phosphate (S1P) is an important lipid mediator that may play a role in IVD degeneration.To study the expression and role of S1PRs in the intervertebal disc (IVD) degeneration to enhance understanding of disc degeneration.Degenerated and normal IVD were harvested from patients through surgery. Expression of S1P receptor subtypes 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 blotting.The nucleus pulposus mainly expressed the S1PR1/2/3, 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.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.