INT224424

Context Info Confidence 0.61 First Reported 2007 Last Reported 2011 Negated 1 Speculated 1 Reported most in Body Documents 12 Total Number 13 Disease Relevance 6.29 Pain Relevance 1.61

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

Anatomy Link Frequency osteoblasts 6 chondrocytes 1 osteoclasts 1 TNFRSF11B (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 38 99.06 Osteoarthritis 398 98.76 Inflammation 40 98.56 Snapping jaw 16 90.64 fibrosis 110 90.60 Bioavailability 14 53.80 Hyperalgesia 2 41.72 Pain 20 41.04 cva 44 5.00 tolerance 12 5.00

Disease Link Frequency Relevance Heat Hypercalcemia 145 99.92 Osteoarthritis 398 98.76 INFLAMMATION 50 98.56 Osteoporosis 432 96.40 Arthropathy 14 92.00 Bone Cancer 25 91.44 Temporomandibular Joint Syndrome 16 90.64 Cystic Fibrosis 110 90.60 Exocrine Pancreatic Insufficiency 5 83.80 Pulmonary Disease 8 82.64

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts.

Regulation (affect) of osteoprotegerin in osteoblasts associated with osteoarthritis

1) Confidence 0.61 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.68 Pain Relevance 0.29

In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts.

Regulation (affect) of OPG in osteoblasts associated with osteoarthritis

2) Confidence 0.61 Published 2007 Journal Arthritis Res Ther Section Abstract Doc Link PMC2246236 Disease Relevance 0.68 Pain Relevance 0.29

GS had no true effect on OPG protein either alone or in combination with vitamin D3.

Neg (no) Regulation (effect) of OPG

3) Confidence 0.53 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0 Pain Relevance 0

The additive effect of both compounds at inhibiting bone resorptive activity could then be explained by the sum of the effect of CS on the OPG and RANKL and the effect of one or both of these compounds on RANKL-independent mechanisms on osteoclastogenesis.

Regulation (effect) of OPG

4) Confidence 0.39 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.33 Pain Relevance 0.04

Nonetheless, it should not be excluded that CS and GS may also act indirectly through the production of other factors that in turn modulate OPG/RANKL and/or resorption activity.

Regulation (modulate) of OPG

5) Confidence 0.27 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.12 Pain Relevance 0.03

Other studies have demonstrated the involvement of the calcium-sensing receptor in the effects of strontium ranelate on osteoblasts, osteoclasts, and OPG/RANKL regulation [126].

Regulation (regulation) of OPG in osteoclasts

6) Confidence 0.25 Published 2010 Journal Osteoporos Int Section Body Doc Link PMC2931762 Disease Relevance 0.35 Pain Relevance 0

We previously showed that patients with OA can be discriminated into two groups classified according to L- or H-OA osteoblasts based on the level of PGE2 production [12,13] and that L-OA osteoblasts (PGE2 levels of less than 2,000 pg/mg protein) were suggested to favor pro-resorptive activity whereas the H-OA osteoblasts favor bone deposition [11,14] To investigate the effects of the compounds on (among other things) the OPG, RANKL, and pro-resorptive activity levels, we chose to perform this study with the L-OA osteoblast specimens.

Spec (investigate) Regulation (effects) of OPG in osteoblasts associated with osteoporosis and osteoarthritis

7) Confidence 0.23 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246236 Disease Relevance 0.99 Pain Relevance 0.37

Given the important role of RANK, RANKL, and OPG in bone metabolism and immune function, it has been suggested that the RANK/RANKL/OPG system and cytokines may work together to cause bone resorption by regulating the RANKL/OPG ratio [35].

Regulation (regulating) of OPG associated with hypercalcemia and cytokine

8) Confidence 0.19 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.24 Pain Relevance 0.12

In addition to these direct effects on osteoblasts and osteoclasts, strontium ranelate also modulates the level of osteoprotegerin (OPG) and RANKL, two molecules strongly involved in the regulation of osteoclastogenesis by osteoblasts.

Regulation (modulates) of OPG in osteoblasts

9) Confidence 0.16 Published 2010 Journal Osteoporos Int Section Body Doc Link PMC2931762 Disease Relevance 0.47 Pain Relevance 0

In addition to these direct effects on osteoblasts and osteoclasts, strontium ranelate also modulates the level of osteoprotegerin (OPG) and RANKL, two molecules strongly involved in the regulation of osteoclastogenesis by osteoblasts.

Regulation (modulates) of osteoprotegerin in osteoblasts

10) Confidence 0.16 Published 2010 Journal Osteoporos Int Section Body Doc Link PMC2931762 Disease Relevance 0.47 Pain Relevance 0

In many previous studies on M-CSF, RANKL, and OPG expression in chondrocytes, the culture periods were brief (24?

Regulation (studies) of OPG in chondrocytes

11) Confidence 0.08 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2829618 Disease Relevance 0.18 Pain Relevance 0.09

Other studies have demonstrated the involvement of the calcium-sensing receptor in the effects of strontium ranelate on osteoblasts, osteoclasts, and OPG/RANKL regulation [126].

Regulation (regulation) of OPG in osteoblasts

12) Confidence 0.08 Published 2010 Journal Osteoporos Int Section Body Doc Link PMC2931762 Disease Relevance 0.35 Pain Relevance 0

The alteration of osteoprotegerin and prostaglandin E2 increases the inflammation-driven bone resorption [2].

Regulation (alteration) of osteoprotegerin associated with inflammation and hypercalcemia

13) Confidence 0.04 Published 2011 Journal Journal of Osteoporosis Section Body Doc Link PMC3010683 Disease Relevance 1.42 Pain Relevance 0.38

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