PMID- 18672387
OWN - NLM
STAT- MEDLINE
DCOM- 20090818
LR  - 20161018
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 17
IP  - 2
DP  - 2009 Feb
TI  - Mevastatin reduces cartilage degradation in rabbit experimental osteoarthritis 
      through inhibition of synovial inflammation.
PG  - 235-43
LID - 10.1016/j.joca.2008.06.012 [doi]
AB  - 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.
FAU - Akasaki, Y
AU  - Akasaki Y
AD  - Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu 
      University, Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Matsuda, S
AU  - Matsuda S
FAU - Nakayama, K
AU  - Nakayama K
FAU - Fukagawa, S
AU  - Fukagawa S
FAU - Miura, H
AU  - Miura H
FAU - Iwamoto, Y
AU  - Iwamoto Y
LA  - eng
PT  - Journal Article
DEP - 20080730
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Interleukin-1beta)
RN  - 1UQM1K0W9X (mevastatin)
RN  - 9LHU78OQFD (Lovastatin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*drug therapy/metabolism/pathology
MH  - Cartilage, Articular/*drug effects/metabolism/pathology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Chondrocytes/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical/methods
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation/drug effects
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use
MH  - Interleukin-1beta/pharmacology
MH  - Lovastatin/*analogs & derivatives/therapeutic use
MH  - Matrix Metalloproteinase 3/biosynthesis/genetics
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Synovial Membrane/drug effects/metabolism/pathology
MH  - Synovitis/metabolism/pathology/*prevention & control
EDAT- 2008/08/02 09:00
MHDA- 2009/08/19 09:00
CRDT- 2008/08/02 09:00
PHST- 2008/01/06 00:00 [received]
PHST- 2008/06/18 00:00 [accepted]
PHST- 2008/08/02 09:00 [pubmed]
PHST- 2009/08/19 09:00 [medline]
PHST- 2008/08/02 09:00 [entrez]
AID - S1063-4584(08)00210-0 [pii]
AID - 10.1016/j.joca.2008.06.012 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2009 Feb;17(2):235-43. doi: 10.1016/j.joca.2008.06.012. 
      Epub 2008 Jul 30.