INT157103

Context Info Confidence 0.59 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 6 Disease Relevance 1.20 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 2 SOX9 (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 139 99.30 metalloproteinase 5 88.80 cINOD 2 71.52 Arthritis 3 66.16 Inflammation 32 57.04 rheumatoid arthritis 16 5.00 cytokine 14 5.00 Pain 6 5.00 dexamethasone 1 5.00 Inflammatory response 1 5.00

Disease Link Frequency Relevance Heat Osteoarthritis 155 99.30 Stress 28 97.48 INFLAMMATION 32 70.96 Apoptosis 34 67.68 Arthritis 5 66.16 Death 5 22.68 Rheumatoid Arthritis 16 5.00 Injury 8 5.00 Obesity 6 5.00 Disease 5 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Physiological tonicity (380 mOsm) during isolation and subsequent passaging of OA HACs significantly increased mRNA levels of both AGC1 (Figure 2a) and SOX9 (Figure 2b) at all passages.

Transcription (levels) of SOX9 associated with osteoarthritis

1) Confidence 0.59 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.25 Pain Relevance 0.13

Physiological tonicity also significantly increased AGC1 (Figure 3a) and SOX9 (Figure 3b) mRNA levels in nonosteoarthritic human articular chondrocytes (NHACs).

Transcription (levels) of SOX9 in chondrocytes

2) Confidence 0.51 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.14 Pain Relevance 0.07

To demonstrate that the hypertonicity-induced chondrogenic marker expression was indeed mediated by NFAT5, we used RNAi to confirm that knockdown of NFAT5 significantly inhibited hypertonic induction of its own transcription as discussed before, significantly suppressed the tonicity-mediated induction of known NFAT5 targets, and, most importantly, significantly eliminated the hypertonicity-mediated mRNA expression of chondrogenic marker genes (COL2, AGC1, SOX9 and COL1).

Transcription (expression) of SOX9

3) Confidence 0.51 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.06 Pain Relevance 0.03

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].

Transcription (levels) of SOX9 in chondrocytes associated with stress

4) Confidence 0.51 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911888 Disease Relevance 0.18 Pain Relevance 0

The results demonstrated: (a) that expression levels of the catabolic genes MMP-3 and MMP-13 were suppressed and (b) mRNA expression levels of anabolic genes of collagen II, SOX9 and aggrecan were increased.

Transcription (expression) of SOX9

5) Confidence 0.49 Published 2009 Journal Phytochemistry Section Abstract Doc Link 19118849 Disease Relevance 0.27 Pain Relevance 0.33

1-integrin was upregulated and Shc, activated ERK 1/2 and the chondrogenic specific transcription factor Sox-9 was highly expressed in MSC cultures treated with IL-1?

Transcription (transcription) of Sox-9

6) Confidence 0.05 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2945017 Disease Relevance 0.30 Pain Relevance 0.03

General Comments

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