INT209893

Context Info Confidence 0.68 First Reported 2006 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 31 Total Number 32 Disease Relevance 11.77 Pain Relevance 4.80

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

Anatomy Link Frequency neutrophils 10 chondrocytes 8 cartilage 6 osteoclast 2 T-cells 2 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 827 100.00 rheumatoid arthritis 373 100.00 Inflammation 358 100.00 Arthritis 146 100.00 cytokine 308 98.68 antagonist 24 95.20 Inflammatory response 2 91.36 Snapping jaw 88 84.80 metalloproteinase 24 60.24 fibrosis 1 55.84

Disease Link Frequency Relevance Heat Osteoarthritis 836 100.00 Rheumatoid Arthritis 373 100.00 Osteoporosis 274 100.00 Arthritis 38 100.00 Endometriosis (extended) 5 99.60 Hypercalcemia 139 99.50 INFLAMMATION 360 99.12 Necrosis 77 95.76 Cancer 89 95.40 Postmenopausal Osteoporosis 17 91.64

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Speculation

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Disease term

CS showed an increased level of OPG expression under either basal conditions (slight) or vitamin D3 induction (p < 0.06).

Positive_regulation (increased) of Gene_expression (expression) of OPG

1) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.21 Pain Relevance 0.05

Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together.

Positive_regulation (upregulated) of Gene_expression (expression) of OPG

2) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.54 Pain Relevance 0.24

The capacity of neutrophils freshly isolated from inflammatory SFs to express large quantities of OPG (Figures 1a and 2c) in comparison to the inferior amount of OPG expressed by healthy blood neutrophils after incubation with certain stimuli (Figure 3) suggests that the induction of OPG expression by neutrophils is regulated by multiple factors.

Positive_regulation (induction) of Gene_expression (expression) of OPG in neutrophils associated with inflammation

3) Confidence 0.61 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.61 Pain Relevance 0.26

Data showed (Figure 2c) that, under basal conditions, the expression ratio of OPG/RANKL was significantly increased when cells were incubated with CS alone and in combination with GS.

Positive_regulation (increased) of Gene_expression (expression) of OPG

4) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.09 Pain Relevance 0.09

Interestingly, in the presence of vitamin D3, CS upregulated OPG expression to a level similar to the one obtained upon treatment with both drugs.

Positive_regulation (upregulated) of Gene_expression (expression) of OPG

5) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.05 Pain Relevance 0.03

Under basal conditions, OPG expression was found to be significantly increased when CS and GS were incubated together.

Positive_regulation (increased) of Gene_expression (expression) of OPG

6) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.29 Pain Relevance 0.09

Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together.

Positive_regulation (incubated) of Gene_expression (expression) of OPG

7) Confidence 0.49 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.54 Pain Relevance 0.24

CS showed an increased level of OPG expression under either basal conditions (slight) or vitamin D3 induction (p < 0.06).

Positive_regulation (level) of Gene_expression (expression) of OPG

8) Confidence 0.46 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.16 Pain Relevance 0.05

SF from patients with RA activates the expression of RANK-L, OPG, and RANK in normal blood neutrophils

Positive_regulation (neutrophils) of Gene_expression (expression) of OPG in neutrophils associated with rheumatoid arthritis

9) Confidence 0.44 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.41 Pain Relevance 0.25

SF from patients with RA activates the expression of RANK-L, OPG, and RANK in normal blood neutrophils

Positive_regulation (activates) of Gene_expression (expression) of OPG in neutrophils associated with rheumatoid arthritis

10) Confidence 0.44 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.40 Pain Relevance 0.25

The significantly increased levels of OPG with CS and GS incubated together appeared to result from the effect of the CS.

Positive_regulation (increased) of Gene_expression (levels) of OPG

11) Confidence 0.40 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

The significantly increased levels of OPG with CS and GS incubated together appeared to result from the effect of the CS.

Positive_regulation (result) of Gene_expression (levels) of OPG

12) Confidence 0.40 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

The exact mechanism (or mechanisms) underlying the synergism that stimulates the neutrophil expression of OPG remains to be elucidated and could be independent of or complementary to the NF-?

Positive_regulation (elucidated) of Gene_expression (expression) of OPG in neutrophil

13) Confidence 0.38 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.49 Pain Relevance 0.16

Differential expression of RANK, RANK-L, and osteoprotegerin by synovial fluid neutrophils from patients with rheumatoid arthritis and by healthy human blood neutrophils Functional links between bone remodeling and the immune system in chronic inflammatory arthritis are mediated, in part, by the ligand of receptor activator of nuclear factor-kappa-B (RANK-L).

Positive_regulation (mediated) of Gene_expression (expression) of osteoprotegerin in neutrophils associated with inflammation, rheumatoid arthritis and arthritis

14) Confidence 0.36 Published 2007 Journal Arthritis Res Ther Section Title Doc Link PMC1906801 Disease Relevance 0.87 Pain Relevance 0.35

In contrast, SFs from patients with osteoarthritis do not induce the expression of OPG and RANK.

Neg (not) Positive_regulation (induce) of Gene_expression (expression) of OPG associated with osteoarthritis

15) Confidence 0.36 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC1906801 Disease Relevance 1.17 Pain Relevance 0.42

-induced increase in RANKL and OPG mRNA expression to control levels.

Positive_regulation (increase) of Gene_expression (expression) of OPG mRNA

16) Confidence 0.34 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

Komuro et al. [4] reported that OPG expression in chondrocytes increased in response to IL-1?

Positive_regulation (increased) of Gene_expression (expression) of OPG in chondrocytes

17) Confidence 0.34 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.19 Pain Relevance 0.09

suppresses the formation of osteoclast-like cells via an increase in OPG production and a decrease in M-CSF production, at least in part, in the human chondrocytes used in this study, and that OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.

Positive_regulation (increase) of Gene_expression (production) of OPG in chondrocytes

18) Confidence 0.30 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.07 Pain Relevance 0

As a result, OPG and RANKL expression increased with IL-1?

Positive_regulation (increased) of Gene_expression (expression) of OPG

19) Confidence 0.25 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.06 Pain Relevance 0.03

-induced increase in RANKL and OPG mRNA expression to control levels.

Positive_regulation (induced) of Gene_expression (expression) of OPG mRNA

20) Confidence 0.25 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

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