INT111156

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Context Info
Confidence 0.58
First Reported 2003
Last Reported 2011
Negated 0
Speculated 1
Reported most in Body
Documents 21
Total Number 24
Disease Relevance 20.08
Pain Relevance 4.27

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 (Dkk1) extracellular region (Dkk1) plasma membrane (Dkk1)
Anatomy Link Frequency
knee 3
synovial fluid 2
plasma 1
joint 1
sacroiliac joints 1
Dkk1 (Mus musculus)
Pain Link Frequency Relevance Heat
endometriosis 13 100.00 Very High Very High Very High
Osteoarthritis 634 99.84 Very High Very High Very High
Arthritis 20 98.32 Very High Very High Very High
spinal inflammation 14 98.08 Very High Very High Very High
antagonist 82 93.20 High High
agonist 13 92.60 High High
rheumatoid arthritis 18 84.56 Quite High
Inflammation 28 81.88 Quite High
cytokine 29 79.68 Quite High
Bile 1 75.68 Quite High
Disease Link Frequency Relevance Heat
Endometriosis (extended) 13 100.00 Very High Very High Very High
Osteoarthritis 634 99.84 Very High Very High Very High
Cancer 311 99.84 Very High Very High Very High
Necrosis 4 99.60 Very High Very High Very High
Osteoporosis 195 99.36 Very High Very High Very High
Metastasis 137 99.34 Very High Very High Very High
Arthropathy 54 98.88 Very High Very High Very High
Multiple Myeloma 52 98.76 Very High Very High Very High
Osteophyte 54 98.68 Very High Very High Very High
Arthritis 20 98.32 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The mechanisms underlying Dkk-1 reduction in the circulation and synovial fluid of OA patients remain to be further investigated.
Negative_regulation (reduction) of Dkk-1 in synovial fluid associated with osteoarthritis
1) Confidence 0.58 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 0.97 Pain Relevance 0.32
Dickkopf-1 (Dkk-1) is a secreted protein that has been defined as a direct inhibitor of Wnt/?
Negative_regulation (inhibitor) of Dkk-1
2) Confidence 0.58 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 0.97 Pain Relevance 0.16
Uderhardt et al. have shown that inhibition of Dkk-1 effectively reduces bone erosion of sacroiliac joints [11].
Negative_regulation (inhibition) of Dkk-1 in sacroiliac joints
3) Confidence 0.58 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 0.85 Pain Relevance 0.25
In addition, there have been no reports in the preclinical modeling studies of increased carcinogenesis in mice treated with agents that block Dkk1 or Sost.
Negative_regulation (block) of Dkk1
4) Confidence 0.55 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.31 Pain Relevance 0
The mechanisms of Dkk-1 reduction in the circulation and synovial fluid of OA patients remain to be investigated further.
Negative_regulation (reduction) of Dkk-1 in synovial fluid associated with osteoarthritis
5) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 1.11 Pain Relevance 0.51
In this study, Dkk-1 levels were decreased in direct relation to the severity of knee OA.
Negative_regulation (decreased) of Dkk-1 in knee associated with osteoarthritis
6) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 1.00 Pain Relevance 0.36
The most intriguing finding in this study has been that concentrations of Dkk-1 were decreased in plasma of patients with primary knee OA compared to the controls.
Negative_regulation (decreased) of Dkk-1 in knee associated with osteoarthritis
7) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 1.10 Pain Relevance 0.48
Therefore, the mild/moderate knee OA patients with high circulating and synovial fluid levels of Dkk-1 may reflect the Dkk-1 capability to inhibit bone remodeling around the osteoarthritic joint.
Spec (may) Negative_regulation (reflect) of Dkk-1 in knee associated with osteoarthritis
8) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 1.13 Pain Relevance 0.41
Furthermore, decreased Dkk-1 levels tend to be essential for osteophyte formation, suggesting that Wnt signaling is a critical initiator for bone formation in the joint.
Negative_regulation (decreased) of Dkk-1 in joint associated with osteophyte
9) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 1.12 Pain Relevance 0.32
One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST).
Negative_regulation (inhibitors) of DKK1
10) Confidence 0.40 Published 2010 Journal Journal of Osteoporosis Section Abstract Doc Link PMC2951123 Disease Relevance 0.24 Pain Relevance 0.04
Here, we focus on two groups of agents; those designed to inhibit the function of Sclerostin and those which block the activity of the DKK1 protein.
Negative_regulation (block) of DKK1 protein
11) Confidence 0.40 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.65 Pain Relevance 0.16
One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST).
Negative_regulation (inhibitors) of Dickkopf-1
12) Confidence 0.40 Published 2010 Journal Journal of Osteoporosis Section Abstract Doc Link PMC2951123 Disease Relevance 0.24 Pain Relevance 0.04
This study has revealed a significant decrease in plasma Dkk-1 of OA patients and illustrated a pronounced inverse correlation with the degree of radiographic severity in patients with primary knee OA.
Negative_regulation (decrease) of Dkk-1 in plasma associated with osteoarthritis
13) Confidence 0.37 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC2989312 Disease Relevance 0.69 Pain Relevance 0.25
Moreover, our data showing that DKK1 treatment inhibits ?
Negative_regulation (inhibits) of DKK1
14) Confidence 0.34 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1950214 Disease Relevance 0.21 Pain Relevance 0
Finally, a small molecule (IIC3; Enzo Biochem) that is capable of binding to and thereby inhibiting the biologic activity of DKK1 is also currently under development.
Negative_regulation (inhibiting) of DKK1
15) Confidence 0.33 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.81 Pain Relevance 0.11
This can be at least partially attributed to decreased Dkk-1-mediated inhibition.


Negative_regulation (inhibition) of Dkk-1-mediated
16) Confidence 0.33 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20039407 Disease Relevance 0 Pain Relevance 0
In that system, Dkk-1 blockade significantly enhanced Wnt signaling in control serum-treated, but not AS serum-treated, Jurkat T cells.
Negative_regulation (blockade) of Dkk-1 in T cells
17) Confidence 0.29 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20039407 Disease Relevance 0 Pain Relevance 0
Nevertheless, it has already been shown that inhibition of Dkk-1 by neutralizing antibodies in MM in vivo [51], [52], or in CaM cells in vitro [53], or by shRNA-mediated interference in CaP cells in vitro [54] is also able to restore bone formation suppressed by neoplastic cells.
Negative_regulation (inhibition) of Dkk-1 associated with cancer, multiple myeloma and reprotox - general 1
18) Confidence 0.23 Published 2011 Journal PLoS ONE Section Body Doc Link PMC3020964 Disease Relevance 2.33 Pain Relevance 0.03
This view is further corroborated by experimental evidence showing that blocking Dkk-1 activity rescues bone formation in animal models of MM [16].
Negative_regulation (blocking) of Dkk-1 associated with multiple myeloma
19) Confidence 0.23 Published 2011 Journal PLoS ONE Section Body Doc Link PMC3020964 Disease Relevance 1.56 Pain Relevance 0.12
Furthermore, Dkk-1 serum levels are elevated in CaM patients with bone metastases, but not in CaM patients with soft tissue metastases, and it has been suggested that Dkk-1-induced inhibition of bone formation may contribute to the osteolytic lesion in CaM [55].
Negative_regulation (inhibition) of Dkk-1-induced associated with cancer and metastasis
20) Confidence 0.17 Published 2011 Journal PLoS ONE Section Body Doc Link PMC3020964 Disease Relevance 2.21 Pain Relevance 0.04

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