INT113282

Context Info Confidence 0.57 First Reported 2003 Last Reported 2011 Negated 0 Speculated 0 Reported most in Body Documents 17 Total Number 17 Disease Relevance 13.71 Pain Relevance 4.17

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

Anatomy Link Frequency osteoblasts 3 TMJ 2 osteoclasts 2 stromal cells 1 neutrophils 1 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat COX-2 inhibitor 23 99.84 Inflammation 136 99.78 Snapping jaw 8 99.56 Osteoarthritis 448 99.38 cytokine 217 98.36 Pain 33 97.16 fibrosis 111 94.08 rheumatoid arthritis 70 92.96 antagonist 24 83.20 Etanercept 16 83.12

Disease Link Frequency Relevance Heat Cancer 245 100.00 INFLAMMATION 142 99.78 Apoptosis 50 99.48 Osteoarthritis 454 99.38 Necrosis 31 99.32 Osteoporosis 270 99.04 Hypercalcemia 72 98.80 Spontaneous Fractures 1 98.04 Osteolysis 48 97.60 Pain 33 97.16

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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

Negative_regulation (decreased) of OCIF in TMJ associated with snapping jaw, osteoporosis and osteoarthritis

1) Confidence 0.57 Published 2003 Journal Int J Oral Maxillofac Surg Section Abstract Doc Link 14505625 Disease Relevance 0.92 Pain Relevance 0.60

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].

Negative_regulation (decreased) of OPG in osteoblasts associated with osteoarthritis

2) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.95 Pain Relevance 0.40

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

Negative_regulation (decreased) of OPG in TMJ associated with snapping jaw, osteoporosis and osteoarthritis

3) Confidence 0.42 Published 2003 Journal Int J Oral Maxillofac Surg Section Abstract Doc Link 14505625 Disease Relevance 0.92 Pain Relevance 0.60

The effect of IL-4 on neutrophil expression of OPG, however, could be associated with the anti-apoptotic function of IL-4 through OPG inhibition of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) produced by human neutrophils [35,36].

Negative_regulation (inhibition) of OPG in neutrophils associated with necrosis, cancer and apoptosis

4) Confidence 0.37 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906801 Disease Relevance 0.73 Pain Relevance 0.22

These findings agree with the recent literature showing that vitamin D3 acts on osteoblasts, thereby increasing RANKL[40] and decreasing OPG[41,42] However, in our study, even though vitamin D3 decreased the OPG/RANKL ratio in favor of osteoclastogenesis, a significant decrease in the resorptive activity was observed.

Negative_regulation (decreasing) of OPG in osteoblasts

5) Confidence 0.37 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.15 Pain Relevance 0.07

Osteoprotegerin (OPG) is a potent inhibitor of osteoclast differentiation and activation, but is limited as a therapeutic agent due to its short circulating half-life.

Negative_regulation (limited) of OPG in osteoclast

6) Confidence 0.24 Published 2004 Journal Exp. Hematol. Section Abstract Doc Link 15050745 Disease Relevance 0.63 Pain Relevance 0.10

However, blocking the OPG/RANK/RANKL pathway with RANK-Fc had no effect on tumor cells in nonosseous sites; the decrease in tumor burden following inhibition of the tumor-mediated osteolysis is an indirect effect secondary to interruption of the vicious cycle of osteolytic metastasis [43-45].

Negative_regulation (decrease) of OPG associated with cancer, osteolysis and metastasis

7) Confidence 0.19 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924520 Disease Relevance 1.59 Pain Relevance 0.03

However, blocking the OPG/RANK/RANKL pathway with RANK-Fc had no effect on tumor cells in nonosseous sites; the decrease in tumor burden following inhibition of the tumor-mediated osteolysis is an indirect effect secondary to interruption of the vicious cycle of osteolytic metastasis [43-45].

Negative_regulation (blocking) of OPG associated with cancer, osteolysis and metastasis

8) Confidence 0.19 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924520 Disease Relevance 1.50 Pain Relevance 0.03

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 (regulation) of osteoprotegerin in stromal cells associated with apoptosis

9) Confidence 0.19 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2963159 Disease Relevance 0.55 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 osteoprotegerin in osteoclasts

10) Confidence 0.19 Published 2008 Journal Clinical Interventions in Aging Section Body Doc Link PMC2682397 Disease Relevance 0.48 Pain Relevance 0.08

1 was upregulated (14.9-fold) and OPG was downregulated (2.8-fold) (both P < 0.001).

Negative_regulation (downregulated) of OPG

11) Confidence 0.17 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911907 Disease Relevance 0.32 Pain Relevance 0.50

OPG is a negative regulator of the RANK/RANKL pathway and prevents RANK-RANKL interaction by sequestering RANKL.

Negative_regulation (regulator) of OPG

12) Confidence 0.17 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1924520 Disease Relevance 0.69 Pain Relevance 0.04

levels remained similar, while OPG levels decreased.

Negative_regulation (decreased) of OPG

13) Confidence 0.13 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2911907 Disease Relevance 0.83 Pain Relevance 0.66

In addition, the loss or reduction in CFTR activity has been shown to lead to chronic inflammation through a decrease in osteoprotegerin and a concomitant increase in prostaglandin E2 [2].

Negative_regulation (decrease) of osteoprotegerin associated with inflammation

14) Confidence 0.09 Published 2011 Journal Journal of Osteoporosis Section Body Doc Link PMC3010683 Disease Relevance 1.42 Pain Relevance 0.41

9), Flt3-ligand, Fractalkine, IGFBPs and Osteoprotegerin were strongly inhibited by COX-2 inhibitor pretreatment demonstrating the specificity of downstream pathways regulated via COX-2 and NF-kB.

Negative_regulation (inhibited) of Osteoprotegerin associated with cox-2 inhibitor

15) Confidence 0.07 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2820536 Disease Relevance 0.64 Pain Relevance 0.25

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 (regulation) of osteoprotegerin in osteoblasts associated with apoptosis

16) Confidence 0.07 Published 2010 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2963159 Disease Relevance 0.55 Pain Relevance 0

Excessive production of RANK ligand and/or osteoprotegerin deficiency may therefore contribute to increased bone resorption.

Negative_regulation (deficiency) of osteoprotegerin associated with hypercalcemia

17) Confidence 0.04 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1526599 Disease Relevance 0.85 Pain Relevance 0.18

General Comments

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