INT123779

Context Info Confidence 0.65 First Reported 2003 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 42 Total Number 44 Disease Relevance 24.30 Pain Relevance 12.45

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

Anatomy Link Frequency chondrocytes 6 cartilage 3 cleavage 2 TMJ 2 scleral cells 1 MMP13 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 524 100.00 COX2 12 100.00 rheumatoid arthritis 192 99.84 Snapping jaw 30 99.84 Osteoarthritis 945 99.64 Inflammation 300 98.28 Arthritis 160 98.24 cytokine 165 96.40 Kinase C 5 91.32 chemokine 19 87.60

Disease Link Frequency Relevance Heat Hypertrophy 45 99.90 Rheumatoid Arthritis 195 99.84 Temporomandibular Joint Syndrome 30 99.84 Hypoxia 27 99.72 Osteoarthritis 948 99.64 Breast Cancer 190 99.60 Apoptosis 155 99.50 Overweight 13 99.40 Arthritis 222 99.24 Atherosclerotic Plaque 1 99.12

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induction of MMP-1 and MMP-13 while having either a very modest effect (MMP-9) or no effect (MMP-2, MMP-3, and MMP-14) on other MMP family members (Figure 2).

Positive_regulation (induction) of MMP-13

1) Confidence 0.65 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.06 Pain Relevance 0.12

The results showed increased MMP-13 immunoreactivity in TMJ diseased disc tissue was correlated with the severity of the histopathological changes.

Positive_regulation (increased) of MMP-13 in TMJ associated with snapping jaw

2) Confidence 0.61 Published 2008 Journal Acta Histochem. Section Abstract Doc Link 18262231 Disease Relevance 0.66 Pain Relevance 0.61

MMP-13 upregulation in disc tissue from patients with TMJ internal derangement suggests that MMP-13 is involved in disc histopathology, and that disc cells actively participate in the synthesis of extracellular matrix-degrading proteinases.

Positive_regulation (upregulation) of MMP-13 in extracellular matrix associated with snapping jaw

3) Confidence 0.61 Published 2008 Journal Acta Histochem. Section Abstract Doc Link 18262231 Disease Relevance 0.60 Pain Relevance 0.56

MMP13 levels are increased in cartilage and synovium of patients with arthritis [30-32].

Positive_regulation (increased) of MMP13 in cartilage associated with arthritis

4) Confidence 0.60 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.99 Pain Relevance 0.37

-stimulated MMP-1 and MMP-13 hnRNA levels (Figure 3b), indicating an effect at the transcriptional level.

Positive_regulation (stimulated) of MMP-13

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

Furthermore, we have shown that plasmin associated with the cell surface is responsible for activating the fibrillar collagenase, MMP-13.

Positive_regulation (activating) of MMP-13

6) Confidence 0.32 Published 2005 Journal Cancer Cell Int Section Body Doc Link PMC548674 Disease Relevance 0.33 Pain Relevance 0.04

High levels of MMPs mRNA and proteins, especially MMP-1, MMP-2, MMP-8, MMP-9, and MMP-13, were shown in human atherosclerotic plaques.

Positive_regulation (levels) of MMP-13 in plaques associated with atherosclerotic plaque and metalloproteinase

7) Confidence 0.29 Published 2010 Journal Atherosclerosis Section Abstract Doc Link 19674746 Disease Relevance 0.65 Pain Relevance 0.62

We additionally established that HNE-modified Col II evoked a significant increase of MMP-13 but inversely to COX-2.

Positive_regulation (increase) of MMP-13

8) Confidence 0.29 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991038 Disease Relevance 0.30 Pain Relevance 0.15

ET-1-induced stimulation of MMP-1 and MMP-13, as well as the induction of iNOS gene expression with subsequent NO overproduction by OA chondrocytes, may interfere with the proinflammatory cytokine pathways.

Positive_regulation (stimulation) of MMP-13 in chondrocytes associated with osteoarthritis and cytokine

9) Confidence 0.28 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.43 Pain Relevance 0.21

The results demonstrated: (a) that expression levels of the catabolic genes MMP-3 and MMP-13 were suppressed and (b) mRNA expression levels of anabolic genes of collagen II, SOX9 and aggrecan were increased.

Positive_regulation (increased) of MMP-13

10) Confidence 0.28 Published 2009 Journal Phytochemistry Section Abstract Doc Link 19118849 Disease Relevance 0.27 Pain Relevance 0.34

That chondrocyte hypertrophy is associated with cartilage degeneration in OA is also supported by the fact that partial deletion of RUNX-2 gene expression, which is believed to account for chondrocyte hypertrophy and MMP-13 upregulation (the two events being closely linked), retards cartilage degeneration in a mouse surgical model [26].

Positive_regulation (upregulation) of MMP-13 in cartilage associated with hypertrophy, metalloproteinase and osteoarthritis

11) Confidence 0.28 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206385 Disease Relevance 1.03 Pain Relevance 0.31

However, our demonstration of a direct requirement of plasmin in the activation of proMMP-13 suggests that this fibrillar collagenase may play a prominent role in the degradative activity of breast cancer cells.

Positive_regulation (activation) of proMMP-13 associated with breast cancer

12) Confidence 0.28 Published 2005 Journal Cancer Cell Int Section Body Doc Link PMC548674 Disease Relevance 0.50 Pain Relevance 0.26

Among all the MMPs, we have recently demonstrated an induction in the synthesis, secretion and activation of two collagenases (MMP-1 and MMP-13) by ET-1 [2].

Positive_regulation (activation) of MMP-13

13) Confidence 0.26 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.47 Pain Relevance 0.19

However, PKA activation seems to be less required for the ET-1-induced upregulation of MMP-13 and not at all necessary for the upregulation of MMP-1 since the inhibition of PKA with KT5720 does not affect the ET-1-induced overproduction of this enzyme.

Positive_regulation (upregulation) of MMP-13

14) Confidence 0.25 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.26 Pain Relevance 0.14

MMP-1 mRNA expression level was stimulated 140-fold, MMP-3 180-fold and MMP-13 170-fold.

Positive_regulation (stimulated) of MMP-13

15) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2212570 Disease Relevance 0 Pain Relevance 0.04

In contrast, others have found that suppression of EP2 expression enhances MMP-13 collagenase induction in human OA chondrocytes [39].

Positive_regulation (induction) of MMP-13 in chondrocytes associated with metalloproteinase and osteoarthritis

16) Confidence 0.21 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206385 Disease Relevance 0.56 Pain Relevance 0.28

By binding to proteins, HNE is capable of activating MMP-13 and increasing the susceptibility of type II collagen (Col II) to proteolytic cleavage by MMP-13 [10].

Positive_regulation (activating) of MMP-13 in cleavage

17) Confidence 0.21 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991038 Disease Relevance 0.83 Pain Relevance 0.31

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

Positive_regulation (increase) of MMP-13

18) Confidence 0.21 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

MMP13 levels are increased in cartilage and synovium of patients with arthritis [30-32].

Positive_regulation (increased) of MMP13 in synovium associated with arthritis

19) Confidence 0.20 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.99 Pain Relevance 0.37

The gene encoding TIMP-2 was induced in chondrocytes obtained from normal or overweight patients while mRNA level of MMP-13 or COX-2 was increased in leptin-treated chondrocytes collected from obese OA patients.

Positive_regulation (increased) of MMP-13 in chondrocytes associated with obesity, osteoarthritis and overweight

20) Confidence 0.20 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911905 Disease Relevance 1.25 Pain Relevance 0.12

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