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

Y. Akasaki, S. Matsuda, K. Nakayama, S. Fukagawa, H. Miura, Y. Iwamoto

Research output: Contribution to journalArticle

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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-1β (IL-1β), 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-1β 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-1β, 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.

Original languageEnglish
Pages (from-to)235-243
Number of pages9
JournalOsteoarthritis and Cartilage
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 1 2009

Fingerprint

Cartilage
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Osteoarthritis
Ligaments
Rabbits
Inflammation
Proteins
Infiltration
Degradation
Matrix Metalloproteinase 3
Chemokine CCL2
Knee
Interleukin-1
Tissue
Intra-Articular Injections
Anterior Cruciate Ligament
Chondrocytes
Linings
Gene expression
Animals

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

Cite this

Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation. / Akasaki, Y.; Matsuda, S.; Nakayama, K.; Fukagawa, S.; Miura, H.; Iwamoto, Y.

In: Osteoarthritis and Cartilage, Vol. 17, No. 2, 01.02.2009, p. 235-243.

Research output: Contribution to journalArticle

Akasaki, Y. ; Matsuda, S. ; Nakayama, K. ; Fukagawa, S. ; Miura, H. ; Iwamoto, Y. / Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis through inhibition of synovial inflammation. In: Osteoarthritis and Cartilage. 2009 ; Vol. 17, No. 2. pp. 235-243.
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