INT335876

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Context Info
Confidence 0.51
First Reported 2010
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 11
Total Number 18
Disease Relevance 6.77
Pain Relevance 0.67

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

extracellular space (Sost) extracellular region (Sost) Golgi apparatus (Sost)
transcription factor binding (Sost)
Anatomy Link Frequency
hip 1
DAN 1
Sost (Mus musculus)
Pain Link Frequency Relevance Heat
spinal stenosis 8 98.36 Very High Very High Very High
Sciatica 8 97.60 Very High Very High Very High
antagonist 30 95.24 Very High Very High Very High
agonist 10 94.64 High High
carpal tunnel syndrome 8 94.52 High High
Inflammation 8 86.08 High High
Pain 10 69.56 Quite High
cINOD 20 18.64 Low Low
Inflammatory response 10 16.96 Low Low
adenocard 10 7.00 Low Low
Disease Link Frequency Relevance Heat
Congenital Anomalies 40 99.44 Very High Very High Very High
Spinal Stenosis 8 98.36 Very High Very High Very High
Nerve Root Compression 8 97.60 Very High Very High Very High
Osteoporosis 148 97.32 Very High Very High Very High
Disease 86 97.12 Very High Very High Very High
Postmenopausal Osteoporosis 10 96.68 Very High Very High Very High
Fracture Healing 90 96.64 Very High Very High Very High
Frailty 8 95.12 Very High Very High Very High
Carpal Tunnel Syndrome 16 94.52 High High
Colitis 18 92.08 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This data shows that pharmacologic inhibition of sclerostin results in increased bone formation, bone mass, and bone strength in rodents.
Negative_regulation (inhibition) of sclerostin
1) Confidence 0.51 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.36 Pain Relevance 0.04
In contrast, inhibition of sclerostin also results in significant bone formation at the periosteal surface.
Negative_regulation (inhibition) of sclerostin
2) Confidence 0.51 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.52 Pain Relevance 0
Thus, loss of Sost may lead to an inability to inactivate the Wnt signaling pathway.
Negative_regulation (loss) of Sost
3) Confidence 0.42 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.35 Pain Relevance 0.03
In addition, there have been no reports in the preclinical modeling studies of increased carcinogenesis in mice treated with agents that block Dkk1 or Sost.
Negative_regulation (block) of Sost
4) Confidence 0.42 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.31 Pain Relevance 0
Based on these characteristics, several pharmaceutical companies have initiated programs to create biological agents that inhibit Sost activity.
Negative_regulation (inhibit) of Sost
5) Confidence 0.42 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.20 Pain Relevance 0
Partly due to its homology to Cerberus and DAN family members, it was originally thought that loss of Sost lead to bone abnormalities primarily due to ectopic activation of BMP pathways [68, 69].
Negative_regulation (loss) of Sost in DAN associated with congenital anomalies
6) Confidence 0.42 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.42 Pain Relevance 0.04
In addition, OsteoGeneX has reportedly developed a small molecule inhibitor of SOST that is in the preclinical development stage [74].
Negative_regulation (inhibitor) of SOST
7) Confidence 0.42 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.21 Pain Relevance 0
In summary, treatments based on inhibition of sclerostin may be a powerful way to restore skeletal bone strength in our patients and may provide more efficacious protection from hip fracture than current therapies as well as potentially improve fracture healing.

3.

Negative_regulation (inhibition) of sclerostin in hip associated with fracture healing and frailty
8) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 1.19 Pain Relevance 0.24
Sclerostin inhibition in primates has recently been reported by Ominsky [15].
Negative_regulation (inhibition) of Sclerostin
9) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.23 Pain Relevance 0.04
Preclinical studies with a sclerostin inhibitor appear to be somewhat different from those with hPTH (1–34).
Negative_regulation (inhibitor) of sclerostin
10) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.52 Pain Relevance 0
Sclerostin suppression is required for balanced remodeling in response to PTH [7].
Negative_regulation (suppression) of Sclerostin
11) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.19 Pain Relevance 0
Although these studies are short term, they suggest that sclerostin inhibition resulting in increased bone formation may be useful clinically in osteoporosis and fracture healing.
Negative_regulation (inhibition) of sclerostin associated with fracture healing and osteoporosis
12) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.41 Pain Relevance 0
Treatment with sclerostin inhibitors is not gender specific; treatment increases bone formation in male mice [14].
Negative_regulation (inhibitors) of sclerostin
13) Confidence 0.37 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2957275 Disease Relevance 0.24 Pain Relevance 0.04
One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST).
Negative_regulation (inhibitors) of Sclerostin
14) Confidence 0.35 Published 2010 Journal Journal of Osteoporosis Section Abstract Doc Link PMC2951123 Disease Relevance 0.24 Pain Relevance 0.04
Amgen reported that an antibody that blocked SOST function increased bone formation, bone strength, and bone mass in a rat model of postmenopausal osteoporosis [75].
Negative_regulation (blocked) of SOST associated with postmenopausal osteoporosis
15) Confidence 0.35 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.24 Pain Relevance 0
One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST).
Negative_regulation (inhibitors) of SOST
16) Confidence 0.35 Published 2010 Journal Journal of Osteoporosis Section Abstract Doc Link PMC2951123 Disease Relevance 0.24 Pain Relevance 0.04
Here, we focus on two groups of agents; those designed to inhibit the function of Sclerostin and those which block the activity of the DKK1 protein.
Negative_regulation (inhibit) of Sclerostin
17) Confidence 0.35 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.64 Pain Relevance 0.16
Amgen, Novartis, and Eli Lilly have all been reported to have developed monoclonal antibodies designed to inhibit SOST [74].
Negative_regulation (inhibit) of SOST
18) Confidence 0.31 Published 2010 Journal Journal of Osteoporosis Section Body Doc Link PMC2951123 Disease Relevance 0.26 Pain Relevance 0

General Comments

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