INT117924

Context Info Confidence 0.72 First Reported 2004 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 2 Total Number 8 Disease Relevance 5.82 Pain Relevance 2.32

cytosol (MAP2K3) nucleoplasm (MAP2K3) signal transduction (MAP2K3)

Anatomy Link Frequency chondrocytes 4 MAP2K3 (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 721 100.00 cytokine 56 92.16 agonist 1 84.32 cINOD 1 77.32 imagery 7 39.80 Immobilon 7 20.12 Inflammation 112 10.24 Arthritis 56 5.00 metalloproteinase 42 5.00 rheumatoid arthritis 28 5.00

Disease Link Frequency Relevance Heat Osteoarthritis 728 100.00 Targeted Disruption 21 100.00 Stress 8 96.12 Colon Cancer 5 79.20 Apoptosis 12 77.60 INFLAMMATION 99 77.08 Arthritis 63 5.00 Disease 35 5.00 Rheumatoid Arthritis 28 5.00 Pain 7 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Expression of MKK3 and MKK6 and their relative contribution to the activation of p38-MAPK isoforms in OA has not been reported.

Gene_expression (Expression) of MKK3 associated with osteoarthritis

1) Confidence 0.72 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.61 Pain Relevance 0.30

Transfection of human OA chondrocytes with MKK3 or MKK6-specific siRNAs knocked down the expression of target proteins and inhibited the IL-1?

Gene_expression (Transfection) of MKK3 in chondrocytes associated with osteoarthritis

2) Confidence 0.72 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.08 Pain Relevance 0.45

-induced activation of p38-MAPK (Figure 2b, c), but the inhibition of phosphorylation was more pronounced when the expression of MKK3 was knocked down compared to the knockdown of MKK6 (Figure 2b).

Gene_expression (expression) of MKK3

3) Confidence 0.63 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.98 Pain Relevance 0.41

Expression and activation of MKK3 and MKK6 in human OA chondrocytes

Gene_expression (Expression) of MKK3 in chondrocytes associated with osteoarthritis

4) Confidence 0.63 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.43 Pain Relevance 0.22

Human OA chondrocytes were transfected with human MKK3 or MKK6-specific siRNAs using On-Target SMART Pools (# L-00350900, L-00396700, Dharmacon RNA Technologies, Lafayette, CO, USA).

Gene_expression (transfected) of MKK3 in chondrocytes associated with osteoarthritis

5) Confidence 0.63 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.22 Pain Relevance 0.11

Next, we investigated the effect of MKK3 or MKK6 knock down on the phosphorylation of p38-MAPK in response to stimulation with IL-1?

Gene_expression (knock) of MKK3 associated with targeted disruption

6) Confidence 0.63 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.09 Pain Relevance 0.45

We then used these antibodies to determine the expression and phosphorylation of MKK3 and MKK6 proteins in human OA chondrocytes.

Spec (determine) Gene_expression (expression) of MKK3 in chondrocytes associated with osteoarthritis

7) Confidence 0.56 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.51 Pain Relevance 0.25

Immunoblots and transcriptional reporter assays using specific inhibitors, as well as expression of constitutively active forms of MEK1 and MKK3, showed that c-IAP2 induction by cAMP is regulated predominantly through ERK1/2 and p38 MAPK and suggested involvement of p90 ribosomal protein S6 kinase and mitogen and stress response kinase-1 as well.

Gene_expression (expression) of MKK3 associated with stress

8) Confidence 0.54 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15078890 Disease Relevance 0.90 Pain Relevance 0.12

General Comments

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