INT129962

Context Info Confidence 0.65 First Reported 2003 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 41 Total Number 42 Disease Relevance 20.74 Pain Relevance 8.54

peptidase activity (MMP13) extracellular space (MMP13) extracellular region (MMP13) Golgi apparatus (MMP13) proteinaceous extracellular matrix (MMP13) lysosome (MMP13)

Anatomy Link Frequency chondrocytes 16 cartilage 4 TMJ 4 scleral cells 2 cleavage 2 MMP13 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 278 100.00 cytokine 166 100.00 Snapping jaw 7 100.00 Inflammatory stimuli 9 99.98 substance P 8 99.98 Osteoarthritis 1125 99.84 Inflammation 271 99.76 Angina 46 98.52 Arthritis 98 98.32 rheumatoid arthritis 166 92.76

Disease Link Frequency Relevance Heat Temporomandibular Joint Syndrome 7 100.00 Osteoarthritis 1097 99.84 Obesity 427 99.84 Aging 78 99.84 INFLAMMATION 302 99.82 Targeted Disruption 7 99.78 Injury 86 98.96 Overweight 53 98.96 Cv General 3 Under Development 12 98.52 Atherosclerotic Plaque 11 98.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

-induced MMP-1 and MMP-13 expression by LG268 requires 12 to 24 hours of pretreatment with LG268 prior to the addition of IL-1?

Positive_regulation (induced) of Gene_expression (expression) of MMP-13

1) Confidence 0.65 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.14 Pain Relevance 0.04

The ability to cleave the collagen triple helix is unique to the collagenases, and the overexpression of MMP-1 and MMP-13 in chondrocytes in response to proinflammatory cytokines such as interleukin-1-beta (IL-1?)

Positive_regulation (overexpression) of Gene_expression (overexpression) of MMP-13 in chondrocytes associated with cytokine

2) Confidence 0.65 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 1.16 Pain Relevance 0.47

Forsyth et al demonstrated that MMP13 expression is increased in aging human chondrocytes and could contribute to cartilage catabolism in osteoarthritis [33].

Positive_regulation (increased) of Gene_expression (expression) of MMP13 in cartilage associated with aging and osteoarthritis

3) Confidence 0.60 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.99 Pain Relevance 0.38

The ability to cleave the collagen triple helix is unique to the collagenases, and the overexpression of MMP-1 and MMP-13 in chondrocytes in response to proinflammatory cytokines such as interleukin-1-beta (IL-1?)

Positive_regulation (as) of Gene_expression (overexpression) of MMP-13 in chondrocytes associated with cytokine

4) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 1.28 Pain Relevance 0.48

A marked increase in MMP-1 and MMP-13 protein was detected in IL-1?

Positive_regulation (increase) of Gene_expression (protein) of MMP-13

5) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

To determine whether this inhibition extended to the level of MMP protein production and enzymatic activity, we performed Western blot analysis of MMP-1 and MMP-13 protein levels in conditioned media and an in vitro collagen destruction assay looking at the breakdown of type I collagen matrix by IL-1?

Positive_regulation (by) of Gene_expression (levels) of MMP-13

6) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

reduced expression of both constructs, which does not reflect the response of endogenous MMP-1 and MMP-13, whose expression is induced by IL-1?

Positive_regulation (by) of Gene_expression (expression) of MMP-13

7) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

-induced MMP-1 and MMP-13 levels when the two ligands were added in combination.

Positive_regulation (induced) of Gene_expression (levels) of MMP-13

8) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0.06

-induced expression of MMP-1 and MMP-13 in rabbit chondrocytes [2,17,18], and administration of these compounds blunts the development of joint disease in animal models of arthritis [18,19].

Positive_regulation (induced) of Gene_expression (expression) of MMP-13 in joint associated with arthropathy and arthritis

9) Confidence 0.47 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.38 Pain Relevance 0.17

Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA.

Positive_regulation (stimulated) of Gene_expression (expression) of MMP-13 mRNA

10) Confidence 0.45 Published 2005 Journal Rheumatology (Oxford) Section Body Doc Link 16148020 Disease Relevance 0 Pain Relevance 0

Gene expression of collagen type-II, collagen type-I, aggrecan, MMP-13, IL-6, Il-1?

Positive_regulation (Gene) of Gene_expression (expression) of MMP-13

11) Confidence 0.43 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.11 Pain Relevance 0

However, changes in both MMP3 and MMP13 gene expression are rapid, dramatic, sustained, and changing during at least the first 48 h of unloaded culture.

Positive_regulation (changes) of Gene_expression (expression) of MMP13

12) Confidence 0.40 Published 2008 Journal J. Orthop. Res. Section Abstract Doc Link 18404723 Disease Relevance 0.36 Pain Relevance 0.10

To elucidate whether MMP-1, MMP-8 and MMP-13 levels in blood were high in patients with unstable angina (UAP), we measured serum MMP-1 and plasma MMP-8 and MMP-13 levels in 45 patients with UAP, 175 with stable coronary artery disease (CAD), and 45 controls.

Spec (whether) Positive_regulation (elucidate) of Spec (whether) Gene_expression (levels) of MMP-13 in blood associated with angina and coronary artery disease

13) Confidence 0.36 Published 2010 Journal Atherosclerosis Section Abstract Doc Link 19674746 Disease Relevance 1.03 Pain Relevance 0.81

We show here that substance P stimulates the production of cartilage-degrading enzymes, such as matrix metalloproteinase-13 (MMP-13), and suppresses proteoglycan deposition in human adult articular chondrocytes via NK(1)-R.

Positive_regulation (stimulates) of Gene_expression (production) of metalloproteinase-13 in chondrocytes associated with metalloproteinase and substance p

14) Confidence 0.34 Published 2008 Journal J. Cell. Physiol. Section Abstract Doc Link 17960584 Disease Relevance 0.15 Pain Relevance 0.54

Here, we demonstrate for the first time that, in cells extracted from human NP tissue, increased levels of p16INK4a were associated with increased gene expression of the degradative enzymes MMP-13 and ADAMTS 5, which is characteristic of disc degeneration [5,39].

Positive_regulation (increased) of Gene_expression (expression) of MMP-13 associated with intervertebral disk degeneration

15) Confidence 0.32 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.45 Pain Relevance 0.07

resulted in upregulation of mRNA and protein expression of collagenases MMP-1 and MMP-13 and the stromelysin MMP-3.

Positive_regulation (upregulation) of Gene_expression (expression) of MMP-13

16) Confidence 0.30 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2212570 Disease Relevance 0.32 Pain Relevance 0.12

stimulation, levels of MMP-1, MMP-3 and MMP-13 production were markedly increased.

Positive_regulation (increased) of Gene_expression (production) of MMP-13

17) Confidence 0.30 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2212570 Disease Relevance 0 Pain Relevance 0

An increase in MMP-13 gene expression was also observed, but only in cells derived from the NP, with significance achieved in cells from non-degenerate discs (P < 0.05) (Fig. 4b).

Positive_regulation (increase) of Gene_expression (expression) of MMP-13

18) Confidence 0.29 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1175026 Disease Relevance 0 Pain Relevance 0

After in vitro chondrogenesis of scleral cells, COL10A, SOX5, IHH, and MMP13 mRNA expressions increased.

Positive_regulation (increased) of Gene_expression (expressions) of MMP13 in scleral cells

19) Confidence 0.28 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2579486 Disease Relevance 0.09 Pain Relevance 0

The effect of ET-1 on MMP-13 production was more sensitive to the inhibitors of protein kinases than on MMP-1 production.

Positive_regulation (effect) of Gene_expression (production) of MMP-13

20) Confidence 0.28 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.47 Pain Relevance 0.15

General Comments

This test has worked.