INT89484

Context Info Confidence 0.76 First Reported 2000 Last Reported 2010 Negated 2 Speculated 7 Reported most in Body Documents 119 Total Number 127 Disease Relevance 53.57 Pain Relevance 19.67

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

Anatomy Link Frequency neutrophils 26 chondrocytes 15 osteoblasts 12 cartilage 6 osteoclast 3 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 1665 100.00 rheumatoid arthritis 2273 99.98 Osteoarthritis 2501 99.62 cINOD 77 99.26 cytokine 963 99.12 Arthritis 450 96.92 Pain 171 96.16 antagonist 73 95.20 endometriosis 5 94.28 psoriasis 102 94.20

Disease Link Frequency Relevance Heat INFLAMMATION 1650 100.00 Rheumatoid Arthritis 2275 99.98 Osteoporosis 918 99.98 Apoptosis 356 99.80 Osteoarthritis 2507 99.62 Targeted Disruption 36 99.60 Hypercalcemia 438 99.52 Cancer 415 99.48 Endometriosis (extended) 21 99.40 Necrosis 400 99.24

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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

Gene_expression (expression) of OPG

1) Confidence 0.76 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.16 Pain Relevance 0.05

Osteoprotegerin and RANKL expression and synthesis

Gene_expression (synthesis) of Osteoprotegerin

2) Confidence 0.76 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.37 Pain Relevance 0.12

We previously demonstrated that OA subchondral bone osteoblasts can be discriminated into two subgroups and that both OPG and RANKL expression levels, and consequently the expression ratio of OPG/RANKL, differ according to the metabolic state of human OA subchondral bone osteoblasts: OPG/RANKL is decreased in L- and increased in H-OA osteoblasts[11].

Gene_expression (expression) of OPG in osteoblasts associated with osteoarthritis

3) Confidence 0.76 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.79 Pain Relevance 0.35

Osteoprotegerin and RANKL expression and synthesis

Gene_expression (expression) of Osteoprotegerin

4) Confidence 0.76 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.37 Pain Relevance 0.12

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

Gene_expression (expression) of OPG

5) Confidence 0.76 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.54 Pain Relevance 0.24

The effect of estrogen was investigated through the expression of RANKL, osteoprotegerin (OPG), M-CSF/CSF-1 and c-fms.

Spec (investigated) Gene_expression (expression) of osteoprotegerin associated with fibromyalgia

6) Confidence 0.75 Published 2008 Journal Int. J. Mol. Med. Section Abstract Doc Link 18506373 Disease Relevance 0.73 Pain Relevance 0.15

The effect of estrogen was investigated through the expression of RANKL, osteoprotegerin (OPG), M-CSF/CSF-1 and c-fms.

Spec (investigated) Gene_expression (expression) of OPG associated with fibromyalgia

7) Confidence 0.75 Published 2008 Journal Int. J. Mol. Med. Section Abstract Doc Link 18506373 Disease Relevance 0.74 Pain Relevance 0.15

We also used human OA chondrocytes to examine the effects of PGE(2) on OPG/RANKL synthesis, examining which surface receptors were affected by PGE(2).

Gene_expression (synthesis) of OPG in chondrocytes

8) Confidence 0.72 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20112374 Disease Relevance 0.16 Pain Relevance 0

The aim of this study was to examine whether nonsteroidal antiinflammatory drug (NSAID) treatment modulates the synthesis of OPG and RANKL in the cartilage of patients with OA, and to investigate whether prostaglandin E(2) (PGE(2)) modifies this system in human OA chondrocytes in culture.

Gene_expression (synthesis) of OPG in cartilage associated with inflammation, cinod and osteoarthritis

9) Confidence 0.72 Published 2010 Journal Arthritis Rheum. Section Abstract Doc Link 20112374 Disease Relevance 0.63 Pain Relevance 0.33

Nonsteroidal antiinflammatory drugs and prostaglandin E(2) modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis.

Gene_expression (synthesis) of osteoprotegerin in cartilage associated with inflammation, knee osteoarthritis and osteoarthritis

10) Confidence 0.72 Published 2010 Journal Arthritis Rheum. Section Title Doc Link 20112374 Disease Relevance 0.47 Pain Relevance 0.31

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.

Gene_expression (expression) of OPG in neutrophils associated with inflammation

11) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.60 Pain Relevance 0.26

Expression of RANK-L, OPG, and RANK proteins by SF neutrophils from patients with RA

Gene_expression (Expression) of OPG in neutrophils associated with rheumatoid arthritis

12) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.46 Pain Relevance 0.23

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.

Gene_expression (expression) of OPG

13) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0 Pain Relevance 0.03

In contrast, PBMLs expressed OPG and RANK from day 0 (Figure 1b) to day 3 (data not shown).

Gene_expression (expressed) of OPG

14) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0 Pain Relevance 0.03

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

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

15) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.40 Pain Relevance 0.25

In contrast, PBMLs cultured under similar conditions secreted RANK-L and OPG in the supernatants (data not shown), confirming that neutrophils and PBMLs expressed RANK-L and OPG differently.

Gene_expression (expressed) of OPG in neutrophils

16) Confidence 0.68 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.32 Pain Relevance 0.20

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

Gene_expression (expression) of OPG

17) Confidence 0.67 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.05 Pain Relevance 0.03

OPG expression (Figure 2a) was not altered by treatment with vitamin D3.

Gene_expression (expression) of OPG

18) Confidence 0.67 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.31 Pain Relevance 0.09

Data from the protein level were almost identical to those from the OPG expression, but CS significantly increased OPG under both basal and vitamin D3 conditions (Figure 2a).

Gene_expression (expression) of OPG

19) Confidence 0.67 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

However, as the protein levels of OPG correspond to its expression levels, one would expect the ratio calculated with the protein to be similar.

Gene_expression (levels) of OPG

20) Confidence 0.67 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.09 Pain Relevance 0.10

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