Arthritis Res Ther. 2009 Aug 20; 11(4): R126Richardson SM, Doyle P, Minogue BM, Gnanalingham K, Hoyland JAABSTRACT: INTRODUCTION: Matrix metalloproteinases (MMPs) are known to be involved in the degradation of the nucleus pulposus (NP) during intervertebral disc (IVD) degeneration. This study investigated MMP-10 (stromelysin-2) expression in the NP during IVD degeneration and correlated its expression with proinflammatory cytokines and molecules involved in innervation and nociception during degeneration which results in low back pain (LBP). METHODS: Human NP tissue was obtained at post-mortem (PM) from patients without a history of back pain and graded as histologically normal or degenerate. Symptomatic degenerate NP samples were also obtained at surgery for LBP. Expression of MMP-10 mRNA and protein was analysed using real-time PCR and immunohistochemistry. Gene expression for proinflammatory cytokines IL-1 and TNF-alpha, nerve growth factor (NGF) and the pain-associated neuropeptide Substance P were also analysed. Correlations between MMP-10 and IL-1, TNF-alpha and NGF were assessed along with NGF with Substance P. RESULTS: MMP-10 mRNA was significantly increased in surgical degenerate NP when compared to PM normal and PM degenerate samples. MMP-10 protein was also significantly higher in degenerate surgical NP samples compared to PM normal. IL-1 and MMP-10 mRNA demonstrated a significant correlation in surgical degenerate samples, while TNF-alpha was not correlated with MMP-10 mRNA. NGF was significantly correlated with both MMP-10 and Substance P mRNA in surgical degenerate NP samples. CONCLUSIONS: MMP-10 expression is increased in the symptomatic degenerate IVD, where it may contribute to matrix degradation and initiation of nociception. Importantly, this study suggests differences in the pathways involved in matrix degradation between painful and pain-free IVD degeneration.
