Background: 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.
Objective: 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 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.
Results: 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.
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.
Keywords: IL-1β; Sphingosine 1-phosphate receptors; intervertebral disc degeneration; nucleus pulposus cells.