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Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation.

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2009年02月
DOI:
10.1016/j.joca.2008.06.012
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
Akasaki Y, Matsuda S, Nakayama K, Fukagawa S, Miura H, Iwamoto Y.
題名:
Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation.
発表情報:
Osteoarthritis Cartilage 2009 Feb. 巻: 17 号: 2 ページ: 235-243
キーワード:
Statin, Osteoarthritis, Cartilage degradation, Synovial inflammation
概要:
抄録:
OBJECTIVE: To examine the therapeutic efficacy of an HMG-CoA reductase inhibitor (statin) in rabbit osteoarthritis (OA) in vitro and in vivo. METHODS: In the presence or absence of mevastatin, rabbit chondrocytes and synoviocytes were incubated with Interleukin-1beta (IL-1beta), and analyzed by biochemical methods. Thirty-two mature rabbits that underwent bilateral anterior cruciate ligament transaction (ACLT) received six consecutive weekly intra-articular injections of mevastatin at three different concentrations or a control solution. All animals were sacrificed 6 weeks after ACLT, and the knee joints were assessed by morphological, histological, immunohistochemical, and biochemical methods. RESULTS: Mevastatin inhibited IL-1beta stimulation of gene expression of monocyte chemoattractant protein-1 (MCP-1) and matrix-metalloproteinases 3 (MMP-3), in synoviocytes but not chondrocytes. The levels of MCP-1 and MMP-3 productions in synoviocytes were significantly reduced by statin-treatment. In rabbit with OA, intra-articular injection of mevastatin significantly reduced cartilage degradation, as assessed by morphological and histological examinations. Synovial tissues of knees treated with mevastatin showed less severe inflammatory responses with reduced thickness of synovial cell lining and less infiltration of subsynovial CD68+monocyte lineage cells compared to untreated control knees. Relative mRNA expressions of MCP-1, IL-1beta, MMP-3, and MMP-13 were reduced in synovial tissues, but not articular cartilage, of knees treated with mevastatin compared with untreated control knees. CONCLUSION: During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.

英語フィールド

Author:
Akasaki Y, Matsuda S, Nakayama K, Fukagawa S, Miura H, Iwamoto Y.
Title:
Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation.
Announcement information:
Osteoarthritis Cartilage 2009 Feb. Vol: 17 Issue: 2 Page: 235-243
Keyword:
Statin, Osteoarthritis, Cartilage degradation, Synovial inflammation
An abstract:
OBJECTIVE: To examine the therapeutic efficacy of an HMG-CoA reductase inhibitor (statin) in rabbit osteoarthritis (OA) in vitro and in vivo. METHODS: In the presence or absence of mevastatin, rabbit chondrocytes and synoviocytes were incubated with Interleukin-1beta (IL-1beta), and analyzed by biochemical methods. Thirty-two mature rabbits that underwent bilateral anterior cruciate ligament transaction (ACLT) received six consecutive weekly intra-articular injections of mevastatin at three different concentrations or a control solution. All animals were sacrificed 6 weeks after ACLT, and the knee joints were assessed by morphological, histological, immunohistochemical, and biochemical methods. RESULTS: Mevastatin inhibited IL-1beta stimulation of gene expression of monocyte chemoattractant protein-1 (MCP-1) and matrix-metalloproteinases 3 (MMP-3), in synoviocytes but not chondrocytes. The levels of MCP-1 and MMP-3 productions in synoviocytes were significantly reduced by statin-treatment. In rabbit with OA, intra-articular injection of mevastatin significantly reduced cartilage degradation, as assessed by morphological and histological examinations. Synovial tissues of knees treated with mevastatin showed less severe inflammatory responses with reduced thickness of synovial cell lining and less infiltration of subsynovial CD68+monocyte lineage cells compared to untreated control knees. Relative mRNA expressions of MCP-1, IL-1beta, MMP-3, and MMP-13 were reduced in synovial tissues, but not articular cartilage, of knees treated with mevastatin compared with untreated control knees. CONCLUSION: During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.


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