INT161840

Context Info Confidence 0.78 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 17 Total Number 20 Disease Relevance 12.44 Pain Relevance 2.63

signal transduction (Tnfrsf11b) extracellular space (Tnfrsf11b) extracellular region (Tnfrsf11b) proteinaceous extracellular matrix (Tnfrsf11b) extracellular matrix organization (Tnfrsf11b)

Anatomy Link Frequency joint 3 chondrocytes 2 osteoblasts 2 osteoclast 2 stromal cells 1 Tnfrsf11b (Rattus norvegicus)

Pain Link Frequency Relevance Heat Arthritis 310 99.28 Osteoarthritis 9 97.34 Snapping jaw 11 97.04 psoriasis 76 93.88 rheumatoid arthritis 60 92.92 cytokine 25 78.80 Inflammation 46 64.88 cINOD 8 60.80 methotrexate 12 58.88 spinal inflammation 11 50.00

Disease Link Frequency Relevance Heat Repression 3 99.92 Hypoxia 13 99.44 Seronegative Spondarthritis 269 99.28 Psoriasis 88 98.68 Multiple Myeloma 55 98.52 Osteoporosis 87 97.48 Calcification 24 97.44 Osteoarthritis 9 97.34 Disease 176 97.12 Temporomandibular Joint Syndrome 11 97.04

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In addition, bone mineral density (BMD) and osteoprotegerin expression in extracted-side condyles were significantly increased while osteoclast numbers were significantly decreased when compared with intact-side condyles.

Gene_expression (expression) of osteoprotegerin in condyles

1) Confidence 0.78 Published 2009 Journal Eur. J. Oral Sci. Section Abstract Doc Link 19627347 Disease Relevance 0.16 Pain Relevance 0.14

Here we demonstrate for the first time that hypoxia-inducible factor-1alpha (Hif-1alpha) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression.

Gene_expression (expression) of Opg in chondrocytes associated with snapping jaw, hypoxia, repression and osteoarthritis

2) Confidence 0.66 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20171183 Disease Relevance 0.78 Pain Relevance 0.35

Here we demonstrate for the first time that hypoxia-inducible factor-1alpha (Hif-1alpha) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression.

Gene_expression (expression) of osteoprotegerin in chondrocytes associated with snapping jaw, hypoxia, repression and osteoarthritis

3) Confidence 0.66 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20171183 Disease Relevance 0.78 Pain Relevance 0.35

In addition, expression of Opg decreased in hypoxia, and Hif-1alpha played a role, in part, in its regulation.

Gene_expression (expression) of Opg associated with hypoxia

4) Confidence 0.66 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20171183 Disease Relevance 0.74 Pain Relevance 0.27

Most likely oestrogen, as well as bisphosphonates, influence the production of OPG and RANKL as demonstrated in in-vitro studies [32,33].

Gene_expression (production) of OPG

5) Confidence 0.45 Published 2010 Journal Nutr J Section Body Doc Link PMC2818614 Disease Relevance 0.28 Pain Relevance 0.05

Although 1,25(OH)2D has been demonstrated in in-vitro studies to increase RANKL expression [5] and reduce the OPG expression [9], supplementation with vitamin D in our study did not significantly affect their serum levels.

Gene_expression (expression) of OPG

6) Confidence 0.45 Published 2010 Journal Nutr J Section Body Doc Link PMC2818614 Disease Relevance 0.17 Pain Relevance 0.03

Therefore, the lack of corresponding changes in serum levels indicate that the circulating levels of OPG and RANKL do not reflect the concentrations in the local tissues [27].

Gene_expression (levels) of OPG

7) Confidence 0.45 Published 2010 Journal Nutr J Section Body Doc Link PMC2818614 Disease Relevance 0.26 Pain Relevance 0.04

This is attributed to increased RANKL production and impaired osteoprotegerin synthesis.

Gene_expression (synthesis) of osteoprotegerin

8) Confidence 0.38 Published 2010 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 20840284 Disease Relevance 0.47 Pain Relevance 0

The osteoblasts also produce OPG which functions as a decoy receptor and binds RANKL and thereby prevents it from binding to RANK [2,7].

Gene_expression (produce) of OPG in osteoblasts

9) Confidence 0.35 Published 2010 Journal Nutr J Section Body Doc Link PMC2818614 Disease Relevance 0.50 Pain Relevance 0

In addition, our study is the first to report that HEP extract stimulated the expression of OPG mRNA but suppressed the expression of RANKL mRNA in the UMR 106 cell line, resulting in a dose-dependent increase in the OPG/RANKL ratio.

Gene_expression (expression) of OPG mRNA

10) Confidence 0.35 Published 2005 Journal Evidence-based Complementary and Alternative Medicine Section Body Doc Link PMC1193542 Disease Relevance 0.23 Pain Relevance 0

As shown in Fig. 5A, HEP extract significantly increased OPG mRNA expression in UMR 106 cells in a dose-dependent manner (P < 0.01).

Gene_expression (expression) of OPG mRNA

11) Confidence 0.35 Published 2005 Journal Evidence-based Complementary and Alternative Medicine Section Body Doc Link PMC1193542 Disease Relevance 0.31 Pain Relevance 0

The RANK ligand (RANKL) and a regulatory protein, osteoprotegerin, produced by stromal cells both bind RANK.

Gene_expression (produced) of osteoprotegerin in stromal cells

12) Confidence 0.29 Published 2010 Journal Advances in Hematology Section Body Doc Link PMC2905716 Disease Relevance 1.07 Pain Relevance 0.04

For example, it has been reported that OPG expression is limited to endothelial cells below the synovial membrane within the psoriatic joint [12]; in contrast, we did not identify reduced circulating OPG concentrations in patients with PsA or a relation between these concentrations and patterns of bone remodeling.

Gene_expression (expression) of OPG in joint associated with psoriasis and arthritis

13) Confidence 0.11 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945067 Disease Relevance 0.52 Pain Relevance 0.17

Intense RANKL expression has been demonstrated within the lining layer in the PsA joint, with more restricted sublining layer OPG expression, implicating imbalance in the RANKL/OPG axis that, in turn, may promote osteoclastogenesis [12].

Gene_expression (expression) of OPG in joint associated with arthritis

14) Confidence 0.10 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945067 Disease Relevance 0.87 Pain Relevance 0.30

For example, it has been reported that OPG expression is limited to endothelial cells below the synovial membrane within the psoriatic joint [12]; in contrast, we did not identify reduced circulating OPG concentrations in patients with PsA or a relation between these concentrations and patterns of bone remodeling.

Gene_expression (concentrations) of OPG in joint associated with psoriasis and arthritis

15) Confidence 0.08 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945067 Disease Relevance 0.56 Pain Relevance 0.18

No overall difference was noted in RANKL or OPG concentrations between the groups of patients with erosive and nonerosive PsA (Figure 1g and 1h).

Gene_expression (concentrations) of OPG associated with arthritis

16) Confidence 0.08 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945067 Disease Relevance 1.47 Pain Relevance 0.68

These proteins are Gla protein, osteoprotegerin, fibrillin I and carbonic anhydrase (all produced by vascular smooth muscle cells).

Gene_expression (produced) of osteoprotegerin in smooth muscle cells

17) Confidence 0.04 Published 2005 Journal BMC Cardiovasc Disord Section Body Doc Link PMC1326214 Disease Relevance 1.29 Pain Relevance 0

In 17 patients with AS, 11 with OA, and 5 controls we performed immunohistochemical analysis of osteoprotegerin (OPG), nuclear factor-kappaB ligand (RANKL), and osteocalcin (OC) expression in osteoblasts and determined the trabecular thickness in AS and OA patients and controls.

Gene_expression (expression) of osteoprotegerin in osteoblasts

18) Confidence 0.02 Published 2010 Journal J. Rheumatol. Section Body Doc Link 20156950 Disease Relevance 0.17 Pain Relevance 0

Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma [5,9-12].

Gene_expression (expression) of osteoprotegerin in osteoclast associated with multiple myeloma

19) Confidence 0.02 Published 2008 Journal Cases J Section Body Doc Link PMC2566563 Disease Relevance 1.73 Pain Relevance 0

Both osteoprotegerin and RANKL can be measured in serum, and the osteoprotegerin/RANKL ratio may be an indicator of osteoclast differentiation and activation.

Gene_expression (measured) of osteoprotegerin in osteoclast

20) Confidence 0.01 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2483438 Disease Relevance 0.08 Pain Relevance 0.03

General Comments

This test has worked.