INT129956

Context Info Confidence 0.72 First Reported 2003 Last Reported 2010 Negated 2 Speculated 4 Reported most in Body Documents 145 Total Number 152 Disease Relevance 60.48 Pain Relevance 26.98

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

Anatomy Link Frequency chondrocytes 30 cartilage 7 joints 4 osteoclasts 3 blood 3 MMP13 (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 4297 100.00 metalloproteinase 1026 100.00 Snapping jaw 14 100.00 cytokine 585 99.82 Inflammatory stimuli 31 99.74 substance P 16 99.68 Inflammation 900 99.64 Angina 82 99.16 COX2 15 98.76 Arthritis 419 98.32

Disease Link Frequency Relevance Heat Osteoarthritis 4324 100.00 Hypertrophy 75 100.00 Temporomandibular Joint Syndrome 14 100.00 Obesity 757 99.84 Targeted Disruption 13 99.78 Hypercalcemia 200 99.66 INFLAMMATION 1011 99.64 Arthritis 596 99.64 Chondrosarcoma 175 99.52 Adhesions 107 99.48

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

ligand rosiglitazone suppresses MMP-1 and MMP13 gene expression more effectively than either compound alone.

Gene_expression (expression) of MMP13

1) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.13 Pain Relevance 0.03

-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].

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

2) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.38 Pain Relevance 0.17

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?)

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

3) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 1.16 Pain Relevance 0.47

As a result, combined treatment should lead to greater inhibition of MMP-1 and MMP-13 gene expression compared with either compound alone.

Gene_expression (expression) of MMP-13

4) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.13 Pain Relevance 0.03

Rosiglitazone and LG268 inhibit MMP-1 and MMP-13 protein production and collagen destruction by SW-1353 cells

Gene_expression (production) of MMP-13

5) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

-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?

Gene_expression (expression) of MMP-13

6) Confidence 0.72 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.14 Pain Relevance 0.04

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

Gene_expression (expression) of MMP-13 mRNA

7) Confidence 0.70 Published 2005 Journal Rheumatology (Oxford) Section Body Doc Link 16148020 Disease Relevance 0 Pain Relevance 0

CONCLUSIONS: Fluoroquinolones show contrasting effects on the expression of the two collagenases MMP-1 and MMP-13, indicating specific effects on MMP gene regulation.

Gene_expression (expression) of MMP-13

8) Confidence 0.70 Published 2005 Journal Rheumatology (Oxford) Section Body Doc Link 16148020 Disease Relevance 0 Pain Relevance 0

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

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

9) Confidence 0.67 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.98 Pain Relevance 0.37

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

Gene_expression (expression) of MMP-13

10) Confidence 0.67 Published 2010 Journal BMC Complement Altern Med Section Body Doc Link PMC2921357 Disease Relevance 0.11 Pain Relevance 0

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.

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

11) Confidence 0.66 Published 2008 Journal J. Cell. Physiol. Section Abstract Doc Link 17960584 Disease Relevance 0.15 Pain Relevance 0.54

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

Gene_expression (protein) of MMP-13

12) Confidence 0.63 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.

Gene_expression (levels) of MMP-13

13) Confidence 0.63 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0.06

, ligands block MMP-1 and MMP-13 gene expression, RXR:PPAR?

Gene_expression (expression) of MMP-13

14) Confidence 0.63 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0.15 Pain Relevance 0.04

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?

Gene_expression (levels) of MMP-13

15) Confidence 0.63 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?

Gene_expression (expression) of MMP-13

16) Confidence 0.63 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 Pain Relevance 0

Previous studies have shown that reporter gene expression driven by components of the MMP-1 and MMP-13 promoters often do not mirror expression of the endogenous genes [20,21].

Gene_expression (expression) of MMP-13

17) Confidence 0.63 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2656243 Disease Relevance 0 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.

Gene_expression (expression) of MMP13

18) Confidence 0.61 Published 2008 Journal J. Orthop. Res. Section Abstract Doc Link 18404723 Disease Relevance 0.35 Pain Relevance 0.10

No gene expression for p16INK4a, MMP-13, or ADAMTS 5 was observed in directly extracted NP cells from non-degenerate discs, but expression for these genes was seen in NP cells directly extracted from degenerate discs (average: p16INK4a, 1,893 copies/100 ng of cDNA; MMP-13, 9,386 copies/100 ng of cDNA; ADAMTS 5, 21,220 copies/100 ng of cDNA).

Gene_expression (expression) of MMP-13

19) Confidence 0.61 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206356 Disease Relevance 0.30 Pain Relevance 0

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.

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

20) Confidence 0.57 Published 2008 Journal J. Cell. Physiol. Section Abstract Doc Link 17960584 Disease Relevance 0.15 Pain Relevance 0.54

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