INT162258

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Context Info
Confidence 0.58
First Reported 2004
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 35
Total Number 40
Disease Relevance 19.14
Pain Relevance 3.55

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular space (COMP) extracellular region (COMP) cell adhesion (COMP)
proteinaceous extracellular matrix (COMP)
Anatomy Link Frequency
chondrocyte 16
ligaments 8
tendons 2
long bone 2
synovium 2
COMP (Homo sapiens)
Pain Link Frequency Relevance Heat
Osteoarthritis 162 100.00 Very High Very High Very High
rheumatoid arthritis 134 100.00 Very High Very High Very High
Arthritis 316 98.04 Very High Very High Very High
Inflammation 59 88.56 High High
imagery 50 81.04 Quite High
psoriasis 114 74.20 Quite High
Lasting pain 28 31.76 Quite Low
Pain 26 23.00 Low Low
metalloproteinase 4 18.80 Low Low
cytokine 8 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Osteoarthritis 164 100.00 Very High Very High Very High
Osteochondrodysplasias 144 100.00 Very High Very High Very High
Rheumatoid Arthritis 134 100.00 Very High Very High Very High
Necrosis 8 99.60 Very High Very High Very High
Targeted Disruption 224 99.40 Very High Very High Very High
Stress 364 99.32 Very High Very High Very High
Cancer 70 99.24 Very High Very High Very High
Aging 28 99.16 Very High Very High Very High
Rheumatic Diseases 38 98.88 Very High Very High Very High
Arthritis 84 98.04 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This result shows that shRNA 3B was equally effective at reducing a wide range of COMP mRNA expression levels.


Negative_regulation (reducing) of Gene_expression (expression) of COMP mRNA
1) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.12 Pain Relevance 0
Overall, we show that suppression of COMP expression by RNAi in vitro would be an effective treatment modality for the PSACH and MED/EDM1 chondrocyte pathology.
Negative_regulation (suppression) of Gene_expression (expression) of COMP in chondrocyte
2) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.46 Pain Relevance 0
COS-7 cells were used to screen and assess the ability of individual shRNAs to reduce COMP expression.
Negative_regulation (reduce) of Gene_expression (expression) of COMP
3) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.35 Pain Relevance 0.03
This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias.
Negative_regulation (reducing) of Gene_expression (expression) of COMP in chondrocytes
4) Confidence 0.51 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2858657 Disease Relevance 0.44 Pain Relevance 0
Moreover, these findings also suggest that surpressing intracellular retention of mutant COMP by reducing COMP expression could be used as a therapeutic approach.
Negative_regulation (reducing) of Gene_expression (expression) of COMP
5) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.53 Pain Relevance 0.04
shRNAs efficiently reduce endogenous COMP expression in human growth plate chondrocytes
Negative_regulation (reduce) of Gene_expression (expression) of COMP in chondrocytes
6) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.12 Pain Relevance 0
The goal of these studies was to determine if reduction in MT-COMP synthesis by the most effective shRNA (3B) can prevent and/or eliminate intracellular retention of COMP and other ECM proteins.
Negative_regulation (reduction) of Gene_expression (synthesis) of MT-COMP
7) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.24 Pain Relevance 0
In these studies, using the COS-7 culture system, long-term decreases in COMP expression were sustainable for up to two weeks in the presence of recombinant COMP (Fig. 4).
Negative_regulation (decreases) of Gene_expression (expression) of COMP
8) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.32 Pain Relevance 0
This is the first study to show that the PSACH cellular phenotype can be mitigated by RNAi reduction of COMP expression.
Negative_regulation (reduction) of Gene_expression (expression) of COMP
9) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.29 Pain Relevance 0
COMP is expressed at high levels during skeletal development and long bone growth and therefore it is important that RNAi therapy be capable of reducing high expression levels of COMP [2], [17], [18].
Negative_regulation (reducing) of Gene_expression (expression) of COMP in long bone
10) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.34 Pain Relevance 0
However, this shRNA retained the ability to reduce COMP expression over time (Fig. 4 A and B).
Negative_regulation (reduce) of Gene_expression (expression) of COMP
11) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.47 Pain Relevance 0
Serum COMP levels were reduced in the glucosamine-treated group after the training period (P=0.012), whereas they did not change in the two other groups.
Negative_regulation (reduced) of Gene_expression (levels) of COMP
12) Confidence 0.47 Published 2010 Journal Osteoarthr. Cartil. Section Body Doc Link 19679221 Disease Relevance 0 Pain Relevance 0
A panel of four shRNAs with predicted homology to different regions of the human COMP mRNA was screened for the ability to reduce COMP expression.
Negative_regulation (reduce) of Gene_expression (expression) of COMP
13) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.22 Pain Relevance 0
We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA.
Negative_regulation (reduce) of Gene_expression (levels) of COMP mRNA
14) Confidence 0.43 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2858657 Disease Relevance 0.42 Pain Relevance 0
As shown in shown in Fig. 6, all four of the shRNAs reduced endogenous human COMP mRNA levels by at least 80%.
Negative_regulation (reduced) of Gene_expression (levels) of COMP mRNA
15) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.05 Pain Relevance 0
shRNAs maintain long-term knock down in the presence of high levels of COMP expression
Negative_regulation (levels) of Gene_expression (expression) of COMP associated with targeted disruption
16) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.88 Pain Relevance 0
We next tested the efficacy of shRNAs to reduce endogenous COMP mRNA levels in human chondrocytes.
Negative_regulation (reduce) of Gene_expression (levels) of COMP mRNA in chondrocytes
17) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.06 Pain Relevance 0
One shRNA (3B) reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels.
Negative_regulation (reduced) of Gene_expression (expression) of recombinant COMP mRNA
18) Confidence 0.38 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2858657 Disease Relevance 0.42 Pain Relevance 0
These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.



Negative_regulation (reduction) of Gene_expression (expression) of COMP
19) Confidence 0.38 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2858657 Disease Relevance 0.33 Pain Relevance 0
Identification of shRNAs that reduce COMP expression
Negative_regulation (reduce) of Gene_expression (expression) of COMP
20) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2858657 Disease Relevance 0.29 Pain Relevance 0.03

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