INT93533

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Context Info
Confidence 0.50
First Reported 2001
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 53
Total Number 54
Disease Relevance 36.93
Pain Relevance 10.53

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

cell differentiation (Tnfsf11) extracellular space (Tnfsf11) extracellular region (Tnfsf11)
plasma membrane (Tnfsf11) intracellular (Tnfsf11) cytoplasm (Tnfsf11)
Anatomy Link Frequency
macrophage 4
osteoblast 3
osteoclast 2
stromal cells 2
MC3T3-E1 2
Tnfsf11 (Mus musculus)
Pain Link Frequency Relevance Heat
Serotonin 16 99.98 Very High Very High Very High
Arthritis 497 99.84 Very High Very High Very High
spinal inflammation 13 99.68 Very High Very High Very High
agonist 32 99.40 Very High Very High Very High
Inflammation 545 99.24 Very High Very High Very High
cytokine 391 98.64 Very High Very High Very High
Snapping jaw 6 98.60 Very High Very High Very High
rheumatoid arthritis 522 98.52 Very High Very High Very High
antagonist 45 97.16 Very High Very High Very High
dexamethasone 2 96.72 Very High Very High Very High
Disease Link Frequency Relevance Heat
Arthritis 539 99.84 Very High Very High Very High
Osteoporosis 252 99.84 Very High Very High Very High
Low Back Pain 14 99.68 Very High Very High Very High
INFLAMMATION 551 99.24 Very High Very High Very High
Peripheral Arterial Disease 217 99.20 Very High Very High Very High
Hypercalcemia 382 99.12 Very High Very High Very High
Metastasis 35 99.08 Very High Very High Very High
Cancer 181 98.78 Very High Very High Very High
Rupture 33 98.72 Very High Very High Very High
Acquired Immune Deficiency Syndrome Or Hiv Infection 221 98.60 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1 cells in a MIP-1alpha concentration-dependent manner.
Positive_regulation (increased) of RANKL mRNA in MC3T3-E1
1) Confidence 0.50 Published 2007 Journal Mol. Cell. Biochem. Section Abstract Doc Link 17549607 Disease Relevance 0.31 Pain Relevance 0.11
When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and RANKL protein expression were increased in these cells.
Positive_regulation (increased) of RANKL mRNA
2) Confidence 0.50 Published 2007 Journal Mol. Cell. Biochem. Section Abstract Doc Link 17549607 Disease Relevance 0.46 Pain Relevance 0.04
This, in turn, upregulates levels of expression of RANKL and interleukin-6, which further exacerbates bone destruction and increases tumor burden [30].
Positive_regulation (upregulates) of RANKL associated with cancer
3) Confidence 0.47 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 1.06 Pain Relevance 0.22
One key factor is the protein receptor activator of nuclear factor-kappa B ligand (RANKL), which is required to induce osteoclastogenesis.
Positive_regulation (activator) of RANKL
4) Confidence 0.45 Published 2002 Journal Drugs Today Section Abstract Doc Link 12532187 Disease Relevance 1.87 Pain Relevance 0.11
OPG activity was detected in the culture medium from indomethacin-treated bones and PTH, PGE2, 1,25D3, and dexamethasone all inhibited the production of OPG activity.
Positive_regulation (detected) of OPG in PGE2 associated with dexamethasone
5) Confidence 0.44 Published 2001 Journal Bone Section Abstract Doc Link 11182380 Disease Relevance 0.23 Pain Relevance 0.12
This induction of RANKL and downregulation of OPG in myeloma cell-BMSC co-cultures is abrogated by neutralizing antibody to ?
Positive_regulation (induction) of RANKL
6) Confidence 0.44 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.65 Pain Relevance 0.15
Whilst RANK and OPG clearly function as upstream components of this signalling pathway, it is presently unclear as to the role(s) played by VCP in osteoclast NF-?
Positive_regulation (Whilst) of OPG in osteoclast
7) Confidence 0.43 Published 2007 Journal BMC Biochem Section Body Doc Link PMC2106369 Disease Relevance 0.13 Pain Relevance 0.04
In fact, RANKL is upregulated in experimental models of arthritis as well as human RA and psoriatic arthritis [11,12,18,19], suggesting that RANKL is a key driving force of osteoclast formation in the joint.
Positive_regulation (upregulated) of RANKL in joint associated with seronegative spondarthritis, rheumatoid arthritis and arthritis
8) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1860063 Disease Relevance 0.94 Pain Relevance 0.51
In addition, the osteoclast activation by IL-1 can be mediated via RANKL upregulation by osteoblast/stromal cells [40].
Positive_regulation (upregulation) of RANKL in stromal cells associated with osteoporosis
9) Confidence 0.42 Published 2001 Journal Arthritis Res Section Body Doc Link PMC128900 Disease Relevance 0.78 Pain Relevance 0.31
At present, the most advanced anti-RANKL approach in clinical development is a fully human monoclonal antibody to RANKL, namely denosumab (Amgen Inc., Thousand Oaks, CA, USA).
Positive_regulation (advanced) of anti-RANKL
10) Confidence 0.41 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 1.60 Pain Relevance 0
Although in VIP treated mice OPG mRNA levels were slightly increased, a seven-fold drop in the RANKL/OPG ratio was observed (Table 3).
Positive_regulation (increased) of OPG
11) Confidence 0.41 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 0.97 Pain Relevance 0.41
The identification of tissue-specific isoforms could increase the importance of sRANKL and OPG in predicting calcified plaque rupture and the dramatic ischemic consequences in the brain and the heart.


1.

Positive_regulation (increase) of OPG in heart associated with rupture
12) Confidence 0.40 Published 2007 Journal Clinical and Developmental Immunology Section Abstract Doc Link PMC2248226 Disease Relevance 0.81 Pain Relevance 0.09
The identification of tissue-specific isoforms could increase the importance of sRANKL and OPG in predicting calcified plaque rupture and the dramatic ischemic consequences in the brain and the heart.


1.

Positive_regulation (increase) of sRANKL in heart associated with rupture
13) Confidence 0.40 Published 2007 Journal Clinical and Developmental Immunology Section Abstract Doc Link PMC2248226 Disease Relevance 0.81 Pain Relevance 0.09
These findings of RANKL induction and concomitant OPG downregulation in bone-derived cells in myeloma were subsequently replicated in other studies involving myeloma cell-BMSC and myeloma cell-osteoblast co-cultures [6,7], although these latter studies and others did not observe an increase in RANKL expression in tumor cells [8].
Positive_regulation (induction) of RANKL in osteoblast associated with cancer and osteoporosis
14) Confidence 0.38 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.66 Pain Relevance 0.03
This may imply that elevated OPG
Positive_regulation (elevated) of OPG
15) Confidence 0.37 Published 2007 Journal Clinical and Developmental Immunology Section Body Doc Link PMC2248226 Disease Relevance 0.65 Pain Relevance 0
Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect.
Positive_regulation (increased) of osteoprotegerin in osteoclast associated with osteoporosis, serotonin and fluoxetine
16) Confidence 0.30 Published 2006 Journal J. Cell. Biochem. Section Abstract Doc Link 16408289 Disease Relevance 0.15 Pain Relevance 1.01
RANKL stimulation simultaneously induces c-Fos-dependent IFN-?
Positive_regulation (stimulation) of RANKL
17) Confidence 0.30 Published 2004 Journal Arthritis Res Ther Section Body Doc Link PMC416442 Disease Relevance 0.87 Pain Relevance 0.30
On the other hand, the RANKL/OPG ratio was strongly enhanced in CIA mice (Table 3).
Positive_regulation (enhanced) of RANKL associated with arthritis
18) Confidence 0.30 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 1.00 Pain Relevance 0.44
On the other hand, the RANKL/OPG ratio was strongly enhanced in CIA mice (Table 3).
Positive_regulation (enhanced) of OPG associated with arthritis
19) Confidence 0.30 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 1.00 Pain Relevance 0.44
RANKL levels are also increased in anti–MDL-1 agonist–treated mice, whereas MDL-1-Ig fusion–treated mice have levels comparable to naive animals.


Positive_regulation (increased) of RANKL associated with agonist
20) Confidence 0.29 Published 2010 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2839155 Disease Relevance 0.36 Pain Relevance 0.21

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