Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc.
BACKGROUND
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 pro-inflammatory cytokines and molecules involved in innervation and nociception during degeneration which results in low back pain (LBP).


METHODS
Human NP tissue was obtained at postmortem (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 polymerase chain reaction and immunohistochemistry. Gene expression for pro-inflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (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.
Richardson
Stephen M
SM
Tissue Injury and Repair Group, School of Clinical and Laboratory Sciences, Stopford Building, The University of Manchester, Oxford Road, Manchester, UK. s.richardson@manchester.ac.uk
Doyle
Paul
P
Minogue
Ben M
BM
Gnanalingham
Kanna
K
Hoyland
Judith A
JA
D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D017116:Low Back Pain / Q000209:etiology / Q000378:metabolism*; D053506:Matrix Metalloproteinase 10 / Q000096:biosynthesis*; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D020932:Nerve Growth Factor; D053506:Matrix Metalloproteinase 10
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