INT108306

Context Info Confidence 0.60 First Reported 2002 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 28 Total Number 28 Disease Relevance 12.74 Pain Relevance 4.46

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

Anatomy Link Frequency cartilage 4 neutrophils 3 TMJ 2 coronary artery 1 osteoblasts 1 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 753 100.00 cytokine 196 99.98 Bioavailability 12 99.96 rheumatoid arthritis 206 99.36 Snapping jaw 32 99.16 Inflammation 218 99.12 cva 13 95.52 Myofascial pain syndrome 2 75.00 antagonist 12 71.52 Cancer pain 1 61.32

Disease Link Frequency Relevance Heat Osteoarthritis 758 100.00 Osteoporosis 295 100.00 Diabetes Mellitus 161 99.84 Endometriosis (extended) 5 99.60 Metastasis 96 99.44 Rheumatoid Arthritis 206 99.36 INFLAMMATION 229 99.12 Temporomandibular Joint Syndrome 32 99.08 Cardiovascular Disease 10 97.76 Celiac Disease 128 97.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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 OPG

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

On the OPG and RANKL system, our data revealed that CS can modulate the expression of these molecules by increasing OPG and decreasing the gene expression level of RANKL, thereby increasing the mRNA ratio of OPG/RANKL.

Positive_regulation (increasing) of OPG

2) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.06 Pain Relevance 0.07

Therefore, one can speculate that extracellular CS may bind the OPG heparin domain, thereby enhancing OPG bioavailability by preventing it from being degraded.

Positive_regulation (enhancing) of OPG associated with bioavailability

3) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0.05

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).

Positive_regulation (increased) of OPG

4) Confidence 0.60 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 (increased) of OPG

5) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

Such CS- and/or GS-independent effects could explain our findings in which, although an increase in the OPG/RANKL ratio is found upon treatment with CS, it appears insufficient to significantly reduce bone resorption.

Positive_regulation (increase) of OPG associated with hypercalcemia

6) Confidence 0.60 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.28 Pain Relevance 0

RESULTS: In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio.

Positive_regulation (increasing) of OPG in cartilage

7) Confidence 0.56 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20112374 Disease Relevance 0.15 Pain Relevance 0

Only EP2/EP4 agonists reproduced the effects of PGE(2) on OPG and RANKL induction.

Positive_regulation (induction) of OPG

8) Confidence 0.56 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20112374 Disease Relevance 0.12 Pain Relevance 0

, and GM-CSF cannot induce neutrophils to express the high concentrations of OPG observed with neutrophils from patients with RA, other factors are involved in inducing OPG.

Positive_regulation (inducing) of OPG in neutrophils associated with rheumatoid arthritis

9) Confidence 0.53 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.76 Pain Relevance 0.25

Prolongation of the incubation time up to 5 days in SM, however, led to an accumulation of OPG in the supernatants of these neutrophils (2.0 ± 0.4 pg/ml, n = 7).

Positive_regulation (accumulation) of OPG in neutrophils

10) Confidence 0.53 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.13 Pain Relevance 0.10

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].

Positive_regulation (increased) of OPG in osteoblasts associated with osteoarthritis

11) Confidence 0.49 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.97 Pain Relevance 0.41

Perhaps, decreased OCIF/OPG concentrations promote osteoclastic activity and induce osteoarthritis of the TMJ.

Positive_regulation (induce) of OCIF in TMJ associated with snapping jaw, osteoporosis and osteoarthritis

12) Confidence 0.49 Published 2003 Journal Int J Oral Maxillofac Surg Section Abstract Doc Link 14505625 Disease Relevance 0.92 Pain Relevance 0.60

Exposure of cells to strontium ranelate in vitro increases the ratio of osteoprotegerin to receptor activator of nuclear factor kappa B ligand (OPG/RANKL) in the medium, while treatment of cells reduces resorption in calvaria [18, 19].

Positive_regulation (activator) of OPG

13) Confidence 0.45 Published 2010 Journal Rheumatol Int Section Body Doc Link PMC2908746 Disease Relevance 0.19 Pain Relevance 0

Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers.

Positive_regulation (activator) of osteoprotegerin

14) Confidence 0.41 Published 2002 Journal Ann. Clin. Biochem. Section Title Doc Link 12564836 Disease Relevance 0.81 Pain Relevance 0.10

However, the expression ratio of OPG/RANKL obtained when cells were treated with GS was not increased.

Neg (not) Positive_regulation (increased) of OPG

15) Confidence 0.40 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0.04

Importantly, under basal conditions, CS and both compounds combined significantly upregulated the expression ratio of OPG/RANKL.

Positive_regulation (upregulated) of OPG

16) Confidence 0.40 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.32 Pain Relevance 0.16

Moreover, the same SF neutrophils obtained from patients with RA and incubated for up to 4 days in CM showed a time-dependent release and accumulation of OPG in supernatants (Figure 2c).

Positive_regulation (accumulation) of OPG in neutrophils associated with rheumatoid arthritis

17) Confidence 0.36 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.72 Pain Relevance 0.36

The OPG/receptor activator of nuclear factor-?

Positive_regulation (activator) of OPG

18) Confidence 0.23 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924520 Disease Relevance 1.14 Pain Relevance 0

-induced increase in OPG levels in human periodontal ligament cells is suppressed through the de novo synthesis of PGE2.

Positive_regulation (increase) of OPG in periodontal ligament

19) Confidence 0.21 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.08 Pain Relevance 0

Deschner et al. [33] reported that fibrochondrocytes constitutively expressed low levels of RANKL, but high levels of OPG; the authors reported that IL-1?

Positive_regulation (levels) of OPG

20) Confidence 0.21 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.21 Pain Relevance 0.10

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