INT184222

Context Info Confidence 0.41 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 7 Total Number 8 Disease Relevance 2.68 Pain Relevance 0.58

signal transduction (SOX9) nucleolus (SOX9) nucleus (SOX9) extracellular matrix organization (SOX9) protein complex assembly (SOX9) protein complex (SOX9)

Anatomy Link Frequency chondrocytes 3 meninges 1 SOX9 (Homo sapiens)

Pain Link Frequency Relevance Heat metalloproteinase 24 97.00 antagonist 15 93.16 Inflammation 28 82.56 cytokine 23 79.44 Osteoarthritis 83 78.88 rheumatoid arthritis 18 78.32 agonist 13 61.68 backache 12 5.00 Pain 8 5.00 Inflammatory response 8 5.00

Disease Link Frequency Relevance Heat Stress 21 97.66 Aging 18 97.48 Campomelic Dysplasia 4 93.64 Cystic Kidney Diseases 1 92.64 Cystic Lymphangioma 1 91.88 Disease 48 86.68 INFLAMMATION 37 82.56 Cyst 11 81.20 Osteoarthritis 98 78.88 Rheumatoid Arthritis 18 78.32

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Mutation

Event

Anatomy

Negation

Speculation

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Although we did not investigate actin stress fiber formation in the present study, they are usually more pronounced in fibroblastic cells and have been shown to suppress SOX9 mRNA levels in chondrocytes [50].

Negative_regulation (suppress) of SOX9 in chondrocytes associated with stress

1) Confidence 0.41 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.18 Pain Relevance 0

Interestingly, while the SOX9 dependency of COL2A1 expression has been unequivocally shown, it may not actually be a key regulator of COL2A1 promoter activity in human adult articular chondrocytes [82].

Negative_regulation (dependency) of SOX9 in chondrocytes

2) Confidence 0.41 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.12 Pain Relevance 0

Gruber et al considered that loss of expression of Sox9 in some of the anulus cell population may play a role in disc aging and degeneration, possibly by decreased modulation of the expression and production of Type II collagen of disc cells 36.

Negative_regulation (loss) of Sox9 associated with aging

3) Confidence 0.35 Published 2008 Journal International Journal of Biological Sciences Section Body Doc Link PMC2532796 Disease Relevance 0.37 Pain Relevance 0

In the developing brain it is expressed in neural crest cells; the very same cells that differentiate into meninges, and animal studies have shown that inactivation of SOX9 in these cells results in craniofacial maldevelopment [25].

Negative_regulation (inactivation) of SOX9 in meninges

4) Confidence 0.34 Published 2010 Journal Cerebrospinal Fluid Res Section Body Doc Link PMC2841093 Disease Relevance 0.83 Pain Relevance 0

SOX6 (usually in combination with SOX9, which was also decreased by IL-1 [albeit not significantly] in this study) determines the chondrogenic phenotype [52].

Negative_regulation (decreased) of SOX9

5) Confidence 0.31 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1175026 Disease Relevance 0 Pain Relevance 0.03

The importance of IL-1 is reinforced by the fact that it has been shown to inhibit chondrogenesis in chondrogenic cells in vitro by downregulation of chondrocyte differentiation state marker genes, such as those encoding SOX9, collagen type II and others, while upregulating NO, prostaglandin E2 and MMP-3, and the finding that the effects could be inhibited by the addition of the IL-1 receptor antagonist (IL-1Ra) [179-181].

Negative_regulation (downregulation) of SOX9 in chondrocyte associated with antagonist and metalloproteinase

6) Confidence 0.20 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2206353 Disease Relevance 1.06 Pain Relevance 0.51

IL-1 treatment of cells derived from non-degenerate discs resulted in a decrease in both SOX6 and SOX9 gene expression.

Negative_regulation (decrease) of SOX9

7) Confidence 0.13 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1175026 Disease Relevance 0 Pain Relevance 0

activation is associated with dedifferentiation and/or COX-2 expression and PGE2 production. 15d-PGJ2-induced inhibition of type II collagen and SOX-9 expression was prevented by the addition of 10 µM BADGE (bisphenol A diglycidyl ether, PPAR-?

Negative_regulation (inhibition) of SOX-9

8) Confidence 0.03 Published 2007 Journal Journal of Korean Medical Science Section Body Doc Link PMC2693859 Disease Relevance 0 Pain Relevance 0.05

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