INT135186

Context Info Confidence 0.58 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 12 Disease Relevance 2.69 Pain Relevance 1.25

cell differentiation (TNFSF11) extracellular space (TNFSF11) extracellular region (TNFSF11) plasma membrane (TNFSF11) intracellular (TNFSF11) response to stress (TNFSF11)

Anatomy Link Frequency chondrocytes 6 cartilage 2 osteoclast 2 TNFSF11 (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 404 97.86 cytokine 42 79.44 Inflammation 44 79.04 Bioavailability 6 74.00 Snapping jaw 24 71.20 Hyperalgesia 3 70.92 Pain 18 70.24 metalloproteinase 3 62.36 COX2 4 10.00 cINOD 7 5.00

Disease Link Frequency Relevance Heat Osteoarthritis 403 97.86 Hypercalcemia 50 85.40 Apoptosis 6 81.68 INFLAMMATION 52 79.04 Osteoporosis 99 78.44 Temporomandibular Joint Syndrome 24 71.20 Hyperalgesia 3 70.92 Pain 18 70.24 Necrosis 8 66.92 Cancer 8 66.56

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The RANKL expression level (Figure 2b) was significantly decreased with CS and with the combination of the two drugs.

Negative_regulation (decreased) of Gene_expression (expression) of RANKL

1) Confidence 0.58 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

Under basal conditions, RANKL expression was significantly reduced by CS and by both drugs incubated together.

Negative_regulation (reduced) of Gene_expression (expression) of RANKL

2) Confidence 0.58 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.39 Pain Relevance 0.17

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

Negative_regulation (decreased) of Gene_expression (synthesis) of RANKL in cartilage

3) Confidence 0.58 Published 2010 Journal Arthritis Rheum. Section Body Doc Link 20112374 Disease Relevance 0.15 Pain Relevance 0

Vitamin D3 significantly decreased the expression ratio of OPG/RANKL.

Negative_regulation (decreased) of Gene_expression (expression) of RANKL

4) Confidence 0.50 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.08 Pain Relevance 0.08

and celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1?

Negative_regulation (inhibitor) of Gene_expression (expression) of RANKL in chondrocytes

5) Confidence 0.44 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.13 Pain Relevance 0.10

(Interestingly, we further showed that L-OA osteoblasts promote osteoclast differentiation and formation and an increase in RANKL levels leading to a decreased OPG/RANKL expression ratio in favor of bone destruction [11].

Negative_regulation (decreased) of Gene_expression (expression) of RANKL in osteoclast associated with osteoarthritis

6) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 1.04 Pain Relevance 0.28

Under vitamin D3, these drugs also showed a decrease in RANKL level, which, however, did not reach statistical significance.

Negative_regulation (decrease) of Gene_expression (level) of RANKL

7) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.33 Pain Relevance 0.16

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.

Negative_regulation (level) of Gene_expression (expression) of RANKL

8) Confidence 0.42 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.06 Pain Relevance 0.07

CONCLUSIONS: The data suggest that baicalin may inhibit RANKL mRNA expression via the suppression of COX-2 expression induced by IL-1beta.

Negative_regulation (inhibit) of Gene_expression (expression) of RANKL mRNA

9) Confidence 0.42 Published 2006 Journal Pharmacology Section Body Doc Link 16636611 Disease Relevance 0 Pain Relevance 0

Baicalin suppressed IL-1beta-induced RANKL and COX-2 production at a concentration of 0.01 microg/ml.

Negative_regulation (suppressed) of Gene_expression (production) of RANKL

10) Confidence 0.42 Published 2006 Journal Pharmacology Section Body Doc Link 16636611 Disease Relevance 0 Pain Relevance 0

not only affected the expression of RANKL, M-CSF, and OPG in chondrocytes, but may also affect the course of cell differentiation.

Negative_regulation (affected) of Gene_expression (expression) of RANKL in chondrocytes

11) Confidence 0.32 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0 Pain Relevance 0

and/or celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1?

Negative_regulation (effect) of Gene_expression (expression) of RANKL in chondrocytes

12) Confidence 0.32 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.51 Pain Relevance 0.39

General Comments

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