INT220243

Context Info Confidence 0.20 First Reported 2007 Last Reported 2007 Negated 0 Speculated 0 Reported most in Abstract Documents 1 Total Number 2 Disease Relevance 0.22 Pain Relevance 0.19

extracellular space (IL1RN, DPEP1) plasma membrane (IL1RN, DPEP1) peptidase activity (DPEP1) extracellular region (IL1RN) nucleus (IL1RN) intracellular (IL1RN)

Anatomy Link Frequency IVD 2 IL1RN (Homo sapiens) DPEP1 (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 10 95.76 antagonist 8 75.00 backache 4 72.64 Sciatica 14 19.76 metalloproteinase 16 5.00 Chronic low back pain 4 5.00

Disease Link Frequency Relevance Heat Disease 8 80.28 Low Back Pain 8 72.64 Arthropathy 2 67.44 Nerve Root Compression 14 19.76 Pressure And Volume Under Development 6 5.00 Musculoskeletal Disease 2 5.00 Apoptosis 2 5.00 Death 2 5.00 Cadaver 2 5.00 Infection 2 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The novel data we are reporting are: direct evidence for MDPs being the major enzymes involved in matrix degradation in the NP, but serine/cysteine proteases having an important role with MDPs in the AF; IL-1Ra and EDTA inhibiting type II collagnease, caseinase and gelatinase activity in the NP; EDTA having limited effects on matrix degrading activity in the AF whereas IL-1Ra almost completely eliminates it; matrix degrading activity correlates with MDP expression in human IVD; IL-1Ra delivered by gene therapy can significantly diminish MDP expression for sustained periods.

IL-1Ra Negative_regulation (diminish) of Gene_expression (expression) of MDP

1) Confidence 0.20 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206387 Disease Relevance 0.22 Pain Relevance 0.07

The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks.

IL-1Ra Negative_regulation (inhibit) of Gene_expression (expression) of MDP in IVD

2) Confidence 0.20 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2206387 Disease Relevance 0 Pain Relevance 0.12

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