INT209900

Context Info Confidence 0.51 First Reported 2007 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 13 Total Number 14 Disease Relevance 4.05 Pain Relevance 1.12

signal transduction (TNFRSF11B) extracellular region (TNFRSF11B) proteinaceous extracellular matrix (TNFRSF11B) extracellular matrix organization (TNFRSF11B)

Anatomy Link Frequency chondrocytes 6 osteoblasts 5 osteoclasts 4 stromal cells 3 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 214 97.86 cytokine 66 93.52 dexamethasone 5 84.56 Inflammation 87 79.04 Snapping jaw 48 72.64 Hyperalgesia 6 72.36 Pain 21 71.68 agonist 3 66.52 metalloproteinase 6 62.36 rheumatoid arthritis 58 50.00

Disease Link Frequency Relevance Heat Apoptosis 28 99.96 Hypercalcemia 62 98.96 Osteoporosis 174 98.06 Osteoarthritis 214 97.86 INFLAMMATION 89 79.04 Temporomandibular Joint Syndrome 48 72.64 Hyperalgesia 6 72.36 Pain 21 71.68 Advanced Or Metastatic Breast Cancer 8 68.00 Necrosis 12 66.92

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Mutation

Event

Anatomy

Negation

Speculation

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Disease term

In these cells, a decrease in the expression of OPG and RANK was observed when incubated in CM and an increase was observed when incubated in SM.

Negative_regulation (decrease) of Gene_expression (expression) of OPG

1) Confidence 0.51 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0 Pain Relevance 0.03

(Interestingly, we further showed that L-OA osteoblasts promote osteoclast differentiation and formation and an increase in RANKL levels leading to a decreased OPG/RANKL expression ratio in favor of bone destruction [11].

Negative_regulation (decreased) of Gene_expression (expression) of OPG in osteoclast associated with osteoarthritis

2) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 1.04 Pain Relevance 0.28

Data showed that vitamin D3 had no effect on the OPG gene expression and protein levels but markedly increased RANKL and, as a result, significantly inhibited the expression ratio of OPG/RANKL.

Negative_regulation (inhibited) of Gene_expression (expression) of OPG

3) Confidence 0.37 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.12 Pain Relevance 0.07

Vitamin D3 significantly decreased the expression ratio of OPG/RANKL.

Negative_regulation (decreased) of Gene_expression (expression) of OPG

4) Confidence 0.37 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.08 Pain Relevance 0.08

and/or celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1?

Negative_regulation (inhibitor) of Gene_expression (expression) of OPG in chondrocytes

5) Confidence 0.25 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.52 Pain Relevance 0.40

, RANKL, M-CSF, and OPG gene expression was unaffected by the presence of celecoxib.

Neg (unaffected) Negative_regulation (unaffected) of Gene_expression (expression) of OPG gene

6) Confidence 0.21 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

, OPG gene expression decreased gradually over 28 days.

Negative_regulation (decreased) of Gene_expression (expression) of OPG gene

7) Confidence 0.21 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

In addition, osteoprotegerin expression is also decreased in osteoblasts and stromal cells in the presence of glucocorticoids.12 Osteoprotegerin plays a counterregulatory role in the effects of RANK-L, and down-regulation of osteoprotegerin also enhances osteoclastogenesis and decreases rates of osteoclast apoptosis.12

Negative_regulation (decreased) of Gene_expression (expression) of osteoprotegerin in stromal cells associated with apoptosis

8) Confidence 0.19 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2963159 Disease Relevance 0.57 Pain Relevance 0

In osteoblasts, RANKL expression increased after stimulation with IL-1, IL-6, and IL-11 [1]; whereas OPG expression decreased [1, 10].

Negative_regulation (decreased) of Gene_expression (expression) of OPG in osteoblasts

9) Confidence 0.18 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.08 Pain Relevance 0.04

and celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1?

Negative_regulation (inhibitor) of Gene_expression (expression) of OPG in chondrocytes

10) Confidence 0.18 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.13 Pain Relevance 0.10

not only affected the expression of RANKL, M-CSF, and OPG in chondrocytes, but may also affect the course of cell differentiation.

Negative_regulation (affected) of Gene_expression (expression) of OPG in chondrocytes

11) Confidence 0.18 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

This, along with the reduction in circulating levels of osteoprotegerin, results in an increase in the number of mature osteoclasts and consequently increased bone breakdown (McCloskey 2006).

Negative_regulation (reduction) of Gene_expression (levels) of osteoprotegerin in osteoclasts

12) Confidence 0.14 Published 2008 Journal Clinical Interventions in Aging Section Body Doc Link PMC2682397 Disease Relevance 0.48 Pain Relevance 0.08

In addition, osteoprotegerin expression is also decreased in osteoblasts and stromal cells in the presence of glucocorticoids.12 Osteoprotegerin plays a counterregulatory role in the effects of RANK-L, and down-regulation of osteoprotegerin also enhances osteoclastogenesis and decreases rates of osteoclast apoptosis.12

Negative_regulation (decreased) of in osteoblasts Gene_expression (expression) of osteoprotegerin in stromal cells associated with apoptosis

13) Confidence 0.07 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2963159 Disease Relevance 0.57 Pain Relevance 0

However, disregulated levels or pharmacological GC use promotes osteopenia and has multiple effects on osteoblasts including decreased proliferation, increased apoptosis, lowered osteoprotegerin (OPN), IL-6, IL-8, and osteocalcin (OCN) expression and elevated 11?

Negative_regulation (lowered) of Gene_expression (expression) of osteoprotegerin in osteoblasts associated with osteoporosis and apoptosis

14) Confidence 0.06 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2958849 Disease Relevance 0.46 Pain Relevance 0.04

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