Abstract | OBJECTIVE: METHODS:
Protein expression was examined by Western blotting or by enzyme-linked immunosorbent assay, and messenger RNA ( mRNA) expression was examined by real-time reverse transcription-polymerase chain reaction analysis. The mediator role of MKP-1 was investigated by using small interfering RNA ( siRNA) methods to down-regulated MKP-1 expression in chondrocytes in culture and by comparing the responses in intact cartilage from MKP-1-deficient and wild-type mice. The effects of aurothiomalate were also confirmed in human rheumatoid cartilage by using tissue samples obtained at the time of total knee replacement surgery. RESULTS: CONCLUSION: Our findings indicate a novel mechanism for the antiinflammatory and antierosive actions of aurothiomalate, through increased expression of MKP-1, which leads to reduced activation of p38 MAPK and suppressed expression of COX-2, MMP-3, and IL-6. The results suggest that manipulation of MKP-1 levels is a promising new mechanism to be directed in the search and development of novel antiinflammatory and antierosive compounds that have the good efficacy of gold compounds but not their toxicity.
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Authors | Riina Nieminen, Riku Korhonen, Teemu Moilanen, Andrew R Clark, Eeva Moilanen |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 62
Issue 6
Pg. 1650-9
(Jun 2010)
ISSN: 1529-0131 [Electronic] United States |
PMID | 20178133
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antirheumatic Agents
- Interleukin-6
- RNA, Messenger
- Gold Sodium Thiomalate
- Cyclooxygenase 2
- p38 Mitogen-Activated Protein Kinases
- Dual Specificity Phosphatase 1
- Matrix Metalloproteinase 3
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Topics |
- Analysis of Variance
- Animals
- Antirheumatic Agents
(pharmacology)
- Blotting, Western
- Cartilage, Articular
(drug effects, metabolism)
- Cells, Cultured
- Chondrocytes
(drug effects, metabolism)
- Cyclooxygenase 2
(genetics, metabolism)
- Dual Specificity Phosphatase 1
(genetics, metabolism)
- Enzyme-Linked Immunosorbent Assay
- Female
- Gene Expression Regulation
- Gold Sodium Thiomalate
(pharmacology)
- Humans
- Interleukin-6
(genetics, metabolism)
- Matrix Metalloproteinase 3
(genetics, metabolism)
- Mice
- Mice, Transgenic
- Phosphorylation
(drug effects, genetics)
- RNA Interference
- RNA, Messenger
(genetics, metabolism)
- Radioimmunoassay
- Reverse Transcriptase Polymerase Chain Reaction
- p38 Mitogen-Activated Protein Kinases
(genetics, metabolism)
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