PMID- 15529384
OWN - NLM
STAT- MEDLINE
DCOM- 20041217
LR  - 20061115
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 50
IP  - 11
DP  - 2004 Nov
TI  - Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix 
      metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in 
      rheumatoid arthritis cartilage.
PG  - 3495-503
AB  - OBJECTIVE: To investigate for the presence of oxidized low-density lipoprotein 
      (ox-LDL) and lectin-like oxidized LDL receptor 1 (LOX-1) in cartilage specimens 
      from rheumatoid arthritis (RA) joints and to determine whether the interaction of 
      ox-LDL with LOX-1 can induce matrix metalloproteinase 3 (MMP-3) in articular 
      cartilage explant culture. METHODS: Human articular cartilage specimens obtained 
      from patients with RA, osteoarthritis (OA), and femoral neck fractures were 
      examined for LOX-1 and ox-LDL by confocal fluorescence microscopy. The 
      association between ox-LDL and LOX-1 was evaluated by immunofluorescence 
      analysis. Articular cartilage specimens from patients with femoral neck fractures 
      were incubated with ox-LDL, with or without preincubation with neutralizing 
      anti-LOX-1 antibody. MMP-3 synthesis by chondrocytes in explant cartilage was 
      evaluated by immunofluorescence, and protein secretion into conditioned medium 
      was monitored by immunoblotting and enzyme-linked immunosorbent assay. RESULTS: 
      The majority of the RA chondrocytes stained positively with both anti-LOX-1 and 
      anti-ox-LDL antibodies; however, no positive cells were found in OA and normal 
      cartilage specimens. Anti-LOX-1 antibody suppressed the binding of DiI-labeled 
      ox-LDL to chondrocytes in explant culture, suggesting that the interaction was 
      mediated by LOX-1. In contrast to native LDL, ox-LDL induced MMP-3 synthesis by 
      articular chondrocytes in association with the induction of LOX-1, which resulted 
      in enhanced secretion of MMP-3 into the culture medium. Anti-LOX-1 antibody 
      reversed ox-LDL-stimulated MMP-3 synthesis to control levels. CONCLUSION: Ox-LDL, 
      principally mediated by LOX-1, enhanced MMP-3 production in articular 
      chondrocytes. Increased accumulation of ox-LDL with elevated expression of LOX-1 
      in RA cartilage indicates a specific role of the receptor-ligand interaction in 
      cartilage pathology in RA.
FAU - Kakinuma, Takumi
AU  - Kakinuma T
AD  - Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 
      54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
FAU - Yasuda, Tadashi
AU  - Yasuda T
FAU - Nakagawa, Takefumi
AU  - Nakagawa T
FAU - Hiramitsu, Teruko
AU  - Hiramitsu T
FAU - Akiyoshi, Miki
AU  - Akiyoshi M
FAU - Akagi, Masao
AU  - Akagi M
FAU - Sawamura, Tatsuya
AU  - Sawamura T
FAU - Nakamura, Takashi
AU  - Nakamura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (OLR1 protein, human)
RN  - 0 (Receptors, LDL)
RN  - 0 (Receptors, Oxidized LDL)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Antibodies/pharmacology
MH  - Arthritis, Rheumatoid/enzymology/*metabolism/pathology
MH  - Cartilage, Articular/enzymology/*metabolism/pathology
MH  - Chondrocytes/drug effects/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoblotting
MH  - Lipoproteins, LDL/antagonists & inhibitors/biosynthesis/*metabolism/pharmacology
MH  - Matrix Metalloproteinase 3/*biosynthesis
MH  - Microscopy, Fluorescence
MH  - Receptors, LDL/immunology/*metabolism
MH  - Receptors, Oxidized LDL
MH  - Scavenger Receptors, Class E
MH  - Tissue Culture Techniques
EDAT- 2004/11/06 09:00
MHDA- 2004/12/18 09:00
CRDT- 2004/11/06 09:00
PHST- 2004/11/06 09:00 [pubmed]
PHST- 2004/12/18 09:00 [medline]
PHST- 2004/11/06 09:00 [entrez]
AID - 10.1002/art.20581 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2004 Nov;50(11):3495-503. doi: 10.1002/art.20581.