Possible involvement of the oxidized low-density lipoprotein/lectin-like oxidized low-density lipoprotein receptor-1 system in pathogenesis and progression of human osteoarthritis

Objective: Using human cartilage samples and cultured chondrocytes, to assess the possible involvement of oxidized low-density lipoprotein (ox-LDL) and lectin-like ox-LDL receptor-1 (LOX-1) in pathogenesis and progression of osteoarthritis (OA). Methods: Thirty-two cartilage samples were obtained from 16 patients with knee OA, and 12 Control samples from six with femoral neck fracture. LOX-1 mRNA expressions in 12 OA and six Control samples were analyzed by reverse transcription-polymerase chain reaction (RTPCR). Immunohistochemistry for ox-LDL and LOX-1 was performed in all samples. The histological CA grade was assessed with the modified Mankin score. The relative percentage of the ox-LDL and LOX-1 immunopositive chondrocytes was calculated in all samples. The effects of ox-LDL on cell viability in cultured human chondrocytes were 5 investigated by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and on proteoglycan synthesis by monitoring [S-35] sulfate incorporation. Results: There was a statistically significant difference between mean LOX-1/GAPDH (LOX-1/human glyceralclehyde-3-phosphate dehydrogenase) ratio of OA samples and that of Control samples (40.6% +/- 10.3 and 11.9% +/- 2.8, respectively, P < 0.0001). The mean percentage of ox-LDL-positive cells was 23.0 +/- 15.7% in OA and 4.3 +/- 3.7% in Control cells (P = 0.0002). The mean percentage of LOX-1-positive cells was 51.7 +/- 29.5% in OA and 10.0 +/- 8.1% in Control cells (P < 0.0001). Both the ox-LDL immunoreactivity and the LOX-1 immunoreactivity were significantly correlated with the modified Mankin scores (R-2 = 0.67 and 0.48, respectively; P < 0.0001 for each). ox-LDL significantly reduced the human chondrocyte viability and proteoglycan synthesis, and pretreatment with anti-human LOX-1 monoclonal antibody reversed these effects. Conclusion: The ox-LDL/LOX-1 system may be involved in human OA. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.