論文 - 詳細
| RRC ID | 43250 |
|---|---|
| 著者 | Nasu Y, Nishida K, Miyazawa S, Komiyama T, Kadota Y, Abe N, Yoshida A, Hirohata S, Ohtsuka A, Ozaki T. |
| タイトル | Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model. |
| ジャーナル | Osteoarthritis Cartilage |
| Abstract |
OBJECTIVE:To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS:CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metalloproteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. RESULTS:In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0mg/kg group than in the control group. TSA suppressed interleukin 1-beta and tumor necrosis factor-alpha-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. CONCLUSION:The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression. |
| 巻・号 | 16(6) |
| ページ | 723-32 |
| 公開日 | 2008-6-1 |
| DOI | 10.1016/j.joca.2007.10.014 |
| PII | S1063-4584(07)00345-7 |
| PMID | 18226559 |
| MeSH | Animals Antirheumatic Agents / therapeutic use Arthritis, Experimental / metabolism Arthritis, Experimental / pathology Arthritis, Experimental / prevention & control* Cartilage, Articular / metabolism Cartilage, Articular / pathology Disease Models, Animal Enzyme Inhibitors / therapeutic use* Gene Expression Regulation / drug effects Histone Deacetylase Inhibitors* Hydroxamic Acids / therapeutic use* Male Matrix Metalloproteinase 13 / biosynthesis Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 3 / biosynthesis Matrix Metalloproteinase 3 / genetics Mice Mice, Inbred DBA RNA, Messenger / genetics Severity of Illness Index Synovitis / metabolism Synovitis / pathology Synovitis / prevention & control* Tissue Inhibitor of Metalloproteinase-1 / biosynthesis Tissue Inhibitor of Metalloproteinase-1 / genetics |
| IF | 4.793 |
| 引用数 | 106 |
| WOS 分野 | ORTHOPEDICS RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |