INT28950

Context Info Confidence 0.69 First Reported 1989 Last Reported 2010 Negated 5 Speculated 9 Reported most in Body Documents 99 Total Number 108 Disease Relevance 46.90 Pain Relevance 16.47

signal transduction (IGF1) extracellular space (IGF1) extracellular region (IGF1)

Anatomy Link Frequency cartilage 24 chondrocytes 18 pituitary 8 blood 6 liver 6 IGF1 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 147 99.90 Inflammation 978 99.84 Clonidine 11 99.84 dexamethasone 34 99.80 qutenza 44 99.68 Neurotransmitter 24 99.48 Pain 420 99.40 rheumatoid arthritis 297 99.40 Arthritis 309 99.32 Osteoarthritis 647 99.20

Disease Link Frequency Relevance Heat Sickle Cell Anemia 25 100.00 Aging 97 99.92 Acromegaly 407 99.86 INFLAMMATION 967 99.84 Osteoporosis 224 99.84 Hypoxia 23 99.84 Targeted Disruption 12 99.84 Hypertrophic Cardiomyopathy 5 99.48 Cancer 650 99.42 Pain 411 99.40

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Both subgroups increased their IGF-1 production similarly in response to PGE2, while the high OA subgroup showed a blunted response to PTH compared to the low OA group.

Positive_regulation (increased) of Gene_expression (production) of IGF-1 in PGE2 associated with osteoarthritis

1) Confidence 0.69 Published 2006 Journal Bone Section Abstract Doc Link 16257278 Disease Relevance 1.46 Pain Relevance 0.62

This is conceptually similar to the approach used in the present study – enhanced autocrine production of IGF-1 and suppression of inhibitory cytokine tone.

Positive_regulation (enhanced) of Gene_expression (production) of IGF-1 associated with cytokine

2) Confidence 0.69 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.10 Pain Relevance 0.09

As IGF-1 is a critical determinant of fertility and fetal development we propose that the actions of Lepidium meyenii are dictated by a central action of the direct, local activation of IGF-1 production in target tissues, independently of growth hormone.

Positive_regulation (activation) of Gene_expression (production) of IGF-1

3) Confidence 0.69 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.22 Pain Relevance 0.07

In vivo, for instance, IGF-I expression is increased during healing of full-thickness cartilage defects [13] and TGF-?

Positive_regulation (increased) of Gene_expression (expression) of IGF-I in cartilage

4) Confidence 0.53 Published 2007 Journal The Open Biomedical Engineering Journal Section Body Doc Link PMC2701085 Disease Relevance 0 Pain Relevance 0

This age-related decline stems both from the decline of growth hormone, which results in reduced liver IGF-1 production as well as a reduction in the ability of skeletal muscle cells to produce IGF-1 locally.

Positive_regulation (results) of Gene_expression (production) of IGF-1 in stems

5) Confidence 0.50 Published 2009 Journal Osteoporos Int Section Body Doc Link PMC2832869 Disease Relevance 0.26 Pain Relevance 0.08

IGF-1 overexpression in transgenic mice has been reported to protect against age-related changes in the neuromuscular junction [38], and in other reports IGF-1 was found to be instrumental in transforming nerve action potential to the release of calcium ion from the sarcoplasmic reticulum [39].

Positive_regulation (overexpression) of Gene_expression (overexpression) of IGF-1 in nerve associated with targeted disruption and action potential

6) Confidence 0.50 Published 2009 Journal Osteoporos Int Section Body Doc Link PMC2832869 Disease Relevance 0.70 Pain Relevance 0.12

Context: Short stature in children may be associated with low IGF-I despite normal stimulated GH levels and without other causes.

Neg (without) Positive_regulation (stimulated) of Gene_expression (levels) of IGF-I associated with growth problems

7) Confidence 0.50 Published 2010 Journal J. Clin. Endocrinol. Metab. Section Abstract Doc Link 19880790 Disease Relevance 0.10 Pain Relevance 0

It is possible that the elevation of IGF-1 production by RNI 249 exerts a negative influence on cartilage catabolism as described with exogenous IGF-1 [54,61-63].

Spec (possible) Positive_regulation (elevation) of Gene_expression (production) of IGF-1 in cartilage

8) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.08 Pain Relevance 0

The potential for RNI 249 to stimulate chondrocyte IGF-1 production was assessed by measurement of IGF-1 in the culture media of cartilage explants.

Positive_regulation (stimulate) of Gene_expression (production) of IGF-1 in cartilage

9) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0 Pain Relevance 0

However, this is the first report that IGF-1 production can be maintained in the face of these otherwise completely suppressive signals.

Positive_regulation (maintained) of Gene_expression (production) of IGF-1 in face

10) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.21 Pain Relevance 0.13

g/ml) partially restored IGF-1 production (P < 0.01) but interestingly the combination fully restored IGF-1 levels to baseline, untreated values despite the continued presence of IL-1?.

Positive_regulation (restored) of Gene_expression (production) of IGF-1

11) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.08 Pain Relevance 0.09

on IGF-1 production

Positive_regulation (on) of Gene_expression (production) of IGF-1

12) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.09 Pain Relevance 0.09

Indeed, there appears to be excellent evidence that growth restriction with chronic inflammation, including arthritis, is the result of suppression of IGF-1 production and activity, independent of GH, and in response to IL-6 [41,42].

Neg (independent) Positive_regulation (independent) of Gene_expression (production) of IGF-1 associated with inflammation and arthritis

13) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.56 Pain Relevance 0.24

Indeed, there appears to be excellent evidence that growth restriction with chronic inflammation, including arthritis, is the result of suppression of IGF-1 production and activity, independent of GH, and in response to IL-6 [41,42].

Positive_regulation (response) of Gene_expression (production) of IGF-1 associated with inflammation and arthritis

14) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.57 Pain Relevance 0.24

g/ml) partially restored IGF-1 production (P < 0.01) but interestingly the combination fully restored IGF-1 levels to baseline, untreated values despite the continued presence of IL-1?.

Positive_regulation (restored) of Gene_expression (production) of IGF-1

15) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.08 Pain Relevance 0.08

While RNI 249 stimulates basal IGF-1 gene expression and production in human cartilage, it was necessary to determine if this action was retained in the presence of IL-1?.

Positive_regulation (stimulates) of Gene_expression (expression) of IGF-1 gene in cartilage

16) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.09 Pain Relevance 0.09

RNI 249 treatment resulted in a dose-dependent increase in IGF-1 levels that were significant at the 50 ?

Positive_regulation (increase) of Gene_expression (levels) of IGF-1

17) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0 Pain Relevance 0

IGF-1 production from human cartilage explants was also enhanced 67% by vincaria alone (10 ?

Positive_regulation (enhanced) of Gene_expression (production) of IGF-1 in cartilage

18) Confidence 0.50 Published 2006 Journal BMC Complement Altern Med Section Body Doc Link PMC1456997 Disease Relevance 0.07 Pain Relevance 0.07

To determine whether this microglial response upregulates astrocytic expression of IGF-related proteins, we induced EAN and used in situ hybridization and immunocytochemistry to examine the mRNAs and peptides for glial fibrillary acidic protein (GFAP), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGFR-I) and IGF binding protein-2 (IGFBP-2).

Spec (whether) Positive_regulation (upregulates) of Gene_expression (expression) of IGF associated with neuritis

19) Confidence 0.49 Published 1995 Journal Brain Pathol. Section Abstract Doc Link 7539325 Disease Relevance 0.40 Pain Relevance 0.46

She had elevated IGF-1 levels of 621 ng/ml, and high to normal GH levels of 3.93 ng/ml.

Positive_regulation (elevated) of Gene_expression (levels) of IGF-1

20) Confidence 0.48 Published 2010 Journal J Med Case Reports Section Body Doc Link PMC2845144 Disease Relevance 0.82 Pain Relevance 0.04

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