INT136555

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Context Info
Confidence 0.55
First Reported 2001
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 31
Total Number 32
Disease Relevance 22.23
Pain Relevance 6.23

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
osteoclast 2
joints 2
macrophage 1
TMJ 1
parathyroid 1
Tnfsf11 (Mus musculus)
Pain Link Frequency Relevance Heat
rheumatoid arthritis 464 100.00 Very High Very High Very High
Inflammation 436 99.52 Very High Very High Very High
Arthritis 516 98.64 Very High Very High Very High
Snapping jaw 6 97.80 Very High Very High Very High
cINOD 29 94.32 High High
Osteoarthritis 35 90.56 High High
chemokine 50 90.08 High High
cytokine 311 86.16 High High
cerebral cortex 1 84.96 Quite High
Hippocampus 1 84.28 Quite High
Disease Link Frequency Relevance Heat
Rheumatoid Arthritis 464 100.00 Very High Very High Very High
Osteoporosis 322 99.84 Very High Very High Very High
Malignant Neoplastic Disease 30 99.72 Very High Very High Very High
Targeted Disruption 22 99.64 Very High Very High Very High
INFLAMMATION 434 99.52 Very High Very High Very High
Hypercalcemia 541 99.44 Very High Very High Very High
Reprotox - General 1 12 99.36 Very High Very High Very High
Disease 163 99.16 Very High Very High Very High
Arthritis 586 98.64 Very High Very High Very High
Cancer 212 98.60 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Interestingly, data from preclinical studies in murine models of humoral hypercalcemia of malignancy suggest that inhibition of RANKL, using OPG-Fc, causes greater suppression of bone resorption and hypercalcemia than do bisphosphonates [41].
Negative_regulation (inhibition) of RANKL associated with malignant neoplastic disease and hypercalcemia
1) Confidence 0.55 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 1.45 Pain Relevance 0.03
Consistent with this, serum OPG levels in myeloma patients are significantly reduced compared with those in healthy control individuals [21].


Negative_regulation (reduced) of serum OPG
2) Confidence 0.48 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.75 Pain Relevance 0.12
Denosumab interferes with RANK signalling by blocking RANKL and, just like OPG, preventing RANK activation.
Negative_regulation (blocking) of RANKL
3) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2374958 Disease Relevance 1.12 Pain Relevance 0.04
Of note, skeletal lesions in these mice were reduced after blockade of RANKL by an OPG analogue [6].
Negative_regulation (blockade) of RANKL
4) Confidence 0.39 Published 2008 Journal Breast Cancer Res Section Body Doc Link PMC2374958 Disease Relevance 1.49 Pain Relevance 0.04
In contrast, inflammation is not affected by the inhibition of RANKL.
Negative_regulation (inhibition) of RANKL associated with inflammation
5) Confidence 0.36 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1860063 Disease Relevance 1.18 Pain Relevance 0.49
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].
Negative_regulation (downregulation) of OPG in osteoblast associated with cancer and osteoporosis
6) Confidence 0.35 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.66 Pain Relevance 0.03
This induction of RANKL and downregulation of OPG in myeloma cell-BMSC co-cultures is abrogated by neutralizing antibody to ?
Negative_regulation (downregulation) of OPG
7) Confidence 0.35 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.65 Pain Relevance 0.15
Nevertheless, whether the predominant source of RANKL in the myeloma bone microenvironment is tumor cells or BMSCs, or both, the consequent exaggerated osteoclast formation and activation is likely to be exacerbated by a concomitant decrease in locally available OPG.
Negative_regulation (decrease) of OPG in osteoclast associated with cancer
8) Confidence 0.35 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924519 Disease Relevance 0.63 Pain Relevance 0.10
were paralleled by a decrease in the number of RANKL- and c-Fos-positive cells.
Negative_regulation (decrease) of RANKL
9) Confidence 0.35 Published 2004 Journal Arthritis Res Ther Section Body Doc Link PMC416442 Disease Relevance 0.47 Pain Relevance 0.15
Excessive production of RANKL and/or a deficiency of OPG could, therefore, contribute to the increased bone resorption typified by the focal bone erosion and bone loss in RA.
Negative_regulation (deficiency) of OPG associated with rheumatoid arthritis and hypercalcemia
10) Confidence 0.35 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 0.85 Pain Relevance 0.36
These data provide evidence that inhibition of RANKL, in this case by its natural inhibitor OPG, can have clinically measurable effects.
Negative_regulation (inhibition) of RANKL
11) Confidence 0.33 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924518 Disease Relevance 0.16 Pain Relevance 0
Secondly, as OPG is a negative regulator of RANK signalling, loss of OPG wild-type function in juvenile hyperphosphatasia is also predicted to promote RANK-NF-?
Negative_regulation (loss) of OPG in juvenile
12) Confidence 0.32 Published 2007 Journal BMC Biochem Section Body Doc Link PMC2106369 Disease Relevance 0.79 Pain Relevance 0
This reduction is accompanied by a large decrease in the RANK-RANKL/OPG ratio.
Negative_regulation (decrease) of OPG
13) Confidence 0.29 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 0.53 Pain Relevance 0.34
In this way, the ratio of RANKL-RANK to OPG that determines the erosive nature of RA is greatly reduced by VIP, accounting for the bone protection achieved by the treatment.
Negative_regulation (reduced) of RANKL-RANK associated with rheumatoid arthritis
14) Confidence 0.29 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1257432 Disease Relevance 0.83 Pain Relevance 0.41
2 is known to decrease RANKL levels and to increase OPG levels, thus interrupting the main osteolysis pathomechanism [15].
Negative_regulation (decrease) of RANKL associated with osteolysis
15) Confidence 0.28 Published 2008 Journal J Orthop Traumatol Section Body Doc Link PMC2657328 Disease Relevance 0.40 Pain Relevance 0
Whether RANKL inhibition is effective at protecting human joints from inflammatory damage remains to be elucidated.
Spec (Whether) Negative_regulation (inhibition) of RANKL in joints associated with inflammation
16) Confidence 0.26 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1860063 Disease Relevance 0.65 Pain Relevance 0.27
Therefore, inhibition of RANKL may have a significant effect on the immunopathogenesis of RA.


Negative_regulation (inhibition) of RANKL associated with rheumatoid arthritis
17) Confidence 0.26 Published 2001 Journal Arthritis Res Section Body Doc Link PMC128900 Disease Relevance 0.56 Pain Relevance 0.21
Moreover, combined use of OPG and parathyroid hormone in ovariectomized rats has shown an additive effect in preventing bone loss, suggesting a potential therapeutic use of intermittent OPG and parathyroid hormone to reverse both generalized and localized bone loss [62].
Negative_regulation (use) of OPG in parathyroid
18) Confidence 0.26 Published 2001 Journal Arthritis Res Section Body Doc Link PMC128900 Disease Relevance 0.52 Pain Relevance 0.32
in the negative regulation of RANKL- and c-Fos-dependent osteoclast differentiation [14].
Negative_regulation (regulation) of RANKL in osteoclast
19) Confidence 0.25 Published 2004 Journal Arthritis Res Ther Section Body Doc Link PMC416442 Disease Relevance 0.42 Pain Relevance 0.17
Role of RANKL inhibition in osteoporosis

When the rate of bone resorption exceeds that of bone formation, destruction of bone tissue occurs, resulting in a fragile skeleton.

Negative_regulation (inhibition) of RANKL in bone tissue associated with hypercalcemia and osteoporosis
20) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Title Doc Link PMC1924518 Disease Relevance 0.52 Pain Relevance 0

General Comments

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