INTRODUCTION: Degeneration of intervertebral disk (IVD) has been considered to be an initial process that leads to chronic lower back pain. Since the extracellular matrix in IVD mainly consists of aggrecan and type I and II collagen fibrils, aggrecanases (ADAMTS‐4 and 5) and collagenases (MMP‐1 and 13) may participate in the tissue degeneration, respectively. Although inhibiting prostaglandin (PG)E2 by a selective cyclooxygenase (COX)‐2 inhibitor has been a favourable treatment for lower back pain, its effect on the IVD degeneration has not been clear. Therefore, the role of the selective COX‐2 inhibitor and PGE2 on the IVD degeneration was investigated by focusing on the regulation of MMPs and ADAMTSs in isolated human IVD cells.
METHODS: Isolated cells from human IVD were stimulated with interleukin (IL)‐1 in the presence or absence of either a selective COX‐2 inhibitor (NS‐398) or exogenous PGE2 for 24 hours. The expressions of MMP‐1 and 13 and ADAMTS‐4 and 5 were quantified by realtime PCR.
RESULTS: IL‐1 induced the expression of both MMPs and ADAMTSs in IVD cells. Treating the cells with NS‐398 inhibited IL‐1 induction of ADAMTS‐4 but not that of MMP‐1, 13 and ADAMTS‐5. On the other hand, treating the cells with exogenous PGE2 resulted in suppression of all MMPs and ADAMTSs tested.
DISCUSSION: Selective COX‐2 inhibitors have been widely used for treating patient with lower back pain. Our results revealed that COX‐2 inhibitor does not seem to prevent IVD degeneration, since IL‐1 inductions of MMPs and ADAMTS‐5 were not influenced by NS‐398. Conversely, the suppression of all MMPs and ADAMTSs expression by exogenous PGE2 suggests that PGE2 has a role in preventing the tissue degeneration by suppressing proteinases expression in IVD cells.