Oxidized LDL binding to LOX-1 enhances MCP-1 expression in cultured human articular chondrocytes

• Published in: Osteoarthritis and cartilage Vol. 17; no. 2; pp. 271 - 275
• Main Authors: Akagi, M., M.D., Ph.D, Ueda, A., M.D, Teramura, T., Ph.D, Kanata, S., M.D, Sawamura, T., M.D., Ph.D, Hamanishi, C., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2009
• Subjects: Cartilage degeneration; Cartilage, Articular - cytology; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Culture Media, Conditioned; Dose-Response Relationship, Drug; Gene Expression; Humans; Interleukin-1beta - pharmacology; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; LOX-1; MCP-1; Oxidized LDL; Reverse Transcriptase Polymerase Chain Reaction - methods; Rheumatology; RNA, Messenger - genetics; Scavenger Receptors, Class E - genetics; Scavenger Receptors, Class E - metabolism; MCP-1; Cartilage degeneration; LOX-1; Oxidized LDL; Chondrocytes
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2008.06.019

Summary Objective It has been suggested that oxidized low-density lipoprotein (ox-LDL) has some roles in progression of osteoarthritis. The purpose of this study is to investigate whether ox-LDL binding to lectin-like ox-LDL receptor 1 (LOX-1) enhances monocyte chemoattractant protein 1 (MCP-1) expression in cultured human articular chondrocytes (HACs). Method The time course and dose response of MCP-1 mRNA expression and MCP-1 protein release into medium following ox-LDL stimulation were investigated using quantitative Real time PCR (delta–delta Ct method) and enzyme-linked immunosorbent assay (ELISA), respectively. To examine the receptor specificity of ox-LDL action, HACs were preincubated with anti-human LOX-1 monoclonal antibody (TS92). Results A time-course study revealed that MCP-1 mRNA expression increased 5.09 ± 0.86 fold 12 h after ox-LDL stimulation compared to time-0. ox-LDL stimulation increased MCP-1 protein level in conditioned medium in a time-dependent manner. Increased MCP-1 level was evident 6 h after stimulation, reaching 830 ± 91 pg/ml at 24 h (33 ± 8 pg/ml at time-0). Dose responses of MCP-1 expression were also evident in mRNA and protein levels. Pretreatment with TS92 markedly suppressed these stimulating effects of ox-LDL, although that with non-specific IgG did not. Native LDL did not affect MCP-1 expression. Conclusion Our results suggest that ox-LDL enhances MCP-1 expression in HACs and supports the hypothesis that ox-LDL is involved in cartilage degeneration.