INT265313

Context Info Confidence 0.66 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 8 Total Number 8 Disease Relevance 2.95 Pain Relevance 0.87

cell differentiation (Tgfbr1) signal transduction (Tgfbr1) cell motility (Tgfbr1) plasma membrane (Tgfbr1) embryo development (Tgfbr1) protein complex (Tgfbr1)

Anatomy Link Frequency chondrocytes 1 endothelial cells 1 medial 1 cartilage 1 fibroblasts 1 Tgfbr1 (Mus musculus)

Pain Link Frequency Relevance Heat Osteoarthritis 364 99.28 fibrosis 41 50.00 metalloproteinase 12 30.60 cytokine 21 22.28 Inflammation 19 5.00 anesthesia 4 5.00 Pain 4 5.00 Arthritis 4 5.00 ketamine 2 5.00 Inflammatory response 2 5.00

Disease Link Frequency Relevance Heat Osteoarthritis 384 99.28 Aging 52 98.72 Disease 62 81.92 Diabetic Retinopathy 1 76.40 Cancer 62 61.20 Immunotherapy Of Cancer 1 58.00 Keloid Scars 20 56.80 Fibrosis 63 50.00 Syndrome 14 49.36 Glaucoma 6 48.68

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

1 activation of ALK5 is growth inhibitory and is thought to mediate vessel stability [10].

Positive_regulation (activation) of ALK5

1) Confidence 0.66 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2659748 Disease Relevance 0.20 Pain Relevance 0

Clearly an increased ALK1/ALK5 ratio in chondrocytes is associated with ageing and OA development [85].

Positive_regulation (increased) of ALK5 in chondrocytes associated with aging and osteoarthritis

2) Confidence 0.34 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.88 Pain Relevance 0.26

A more than threefold increase in the ALK1/ALK5 ratio was observed on the medial side while the ratio on the lateral side was unaffected.

Positive_regulation (increase) of ALK5 in medial

3) Confidence 0.34 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.95 Pain Relevance 0.28

As measured by quantitative real-time RT-PCR, the transcripts of Col1a2, Ctgf and SPARC showed increased expression in the fibroblasts from TBR1CA; Cre-ER mice injected with 4-OHT, in which Tgfbr1 was constitutively active, compared with those in the cells from TBR1CA; Cre-ER mice injected with oil (Figure 1).

Positive_regulation (active) of Tgfbr1 in fibroblasts

4) Confidence 0.33 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888211 Disease Relevance 0 Pain Relevance 0

In endothelial cells, but also in chondrocytes, activation of the ALK5 route is followed by Smad2 or Smad3 phosphorylation while ALK1 has been found to result in phosphorylation of Smad1, Smad5, or Smad8 [29-31].

Positive_regulation (activation) of ALK5 in endothelial cells

5) Confidence 0.23 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.30 Pain Relevance 0.09

In cartilage of ageing mice and in experimental OA models we have found that the ALK1/ALK5 ratio is significantly increased, favoring TGF?

Positive_regulation (increased) of ALK5 in cartilage associated with aging and osteoarthritis

6) Confidence 0.23 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2875624 Disease Relevance 0.56 Pain Relevance 0.23

The activated ALK-5 in turn phosphorylates and activates transcription factors Smad2/3 [4,5].

Positive_regulation (activated) of ALK-5

7) Confidence 0.09 Published 2010 Journal Molecular Vision Section Body Doc Link PMC2956700 Disease Relevance 0.06 Pain Relevance 0

Goumans et al. revealed that the inhibitor of DNA binding 1 (ID-1), a helix-loop-helix (HLH) protein that can form heterodimers with members of the basic HLH family of transcription factors, is a specific downstream signal of ALK-1, whereas the proteinase inhibitor plasminogen activator inhibitor-1 (PAI-1) is induced by ALK-5 activation [68].

Positive_regulation (activation) of ALK-5

8) Confidence 0.08 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2871186 Disease Relevance 0 Pain Relevance 0

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