Tags

Type your tag names separated by a space and hit enter

Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage.
Arthritis Rheum. 2004 Nov; 50(11):3495-503.AR

Abstract

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.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15529384

Citation

Kakinuma, Takumi, et al. "Lectin-like Oxidized Low-density Lipoprotein Receptor 1 Mediates Matrix Metalloproteinase 3 Synthesis Enhanced By Oxidized Low-density Lipoprotein in Rheumatoid Arthritis Cartilage." Arthritis and Rheumatism, vol. 50, no. 11, 2004, pp. 3495-503.
Kakinuma T, Yasuda T, Nakagawa T, et al. Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage. Arthritis Rheum. 2004;50(11):3495-503.
Kakinuma, T., Yasuda, T., Nakagawa, T., Hiramitsu, T., Akiyoshi, M., Akagi, M., Sawamura, T., & Nakamura, T. (2004). Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage. Arthritis and Rheumatism, 50(11), 3495-503.
Kakinuma T, et al. Lectin-like Oxidized Low-density Lipoprotein Receptor 1 Mediates Matrix Metalloproteinase 3 Synthesis Enhanced By Oxidized Low-density Lipoprotein in Rheumatoid Arthritis Cartilage. Arthritis Rheum. 2004;50(11):3495-503. PubMed PMID: 15529384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage. AU - Kakinuma,Takumi, AU - Yasuda,Tadashi, AU - Nakagawa,Takefumi, AU - Hiramitsu,Teruko, AU - Akiyoshi,Miki, AU - Akagi,Masao, AU - Sawamura,Tatsuya, AU - Nakamura,Takashi, PY - 2004/11/6/pubmed PY - 2004/12/18/medline PY - 2004/11/6/entrez SP - 3495 EP - 503 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 50 IS - 11 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/15529384/Lectin_like_oxidized_low_density_lipoprotein_receptor_1_mediates_matrix_metalloproteinase_3_synthesis_enhanced_by_oxidized_low_density_lipoprotein_in_rheumatoid_arthritis_cartilage_ L2 - https://doi.org/10.1002/art.20581 DB - PRIME DP - Unbound Medicine ER -