Effects of Hyperlipidemia on Progression of Knee Osteoarthritis

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【Purpose】 Recently, it has been demonstrated in in-vivo and vitro studies that lectin-like oxidized low-density lipoprotein LDL (ox-LDL) receptor-1 (LOX-1) expresses on articular chondrocytes and suggested that its ligand ox-LDL plays some roles in degeneration of articular cartilage. The purpose of this study is to examine effects of hyperlipidemic loading on articular cartilage degeneration using a congenital hyperlipidemic rabbit (KHC).【Methods】 Japanese white rabbits (JW, n=6) and KHC rabbits (n=6) underwent transection of the anterior cruciate ligament and excision of the medial meniscus in the right knee. Sham operation was performed in the left knee. All animals were killed at 8 weeks following the surgery. The weight-bearing areas of the medial femoral condyle were subjected to histological evaluation according to the modified Mankin scoring system. Furthermore, these were subjected to LOX-1, ox-LDL and basic fibroblast growth factor (bFGF) immunohistochemical staining. To exam … More ine effect of ox-LDL on bFGF expression in chondrocytes rabbit articular chondrocytes (RACs) were stimulated with ox-LDL (0, 50, 100 μg/m1) and bFGF mRNA expression was investigated with RT-PCR. To know whether the effect is mediated by LOX-1, cells were pre-incubated with anti-human LOX-1 antibody (JTX92, 50 μg/m1), and then stimulated with ox-LDL at various concentrations.【Results】 Mean Mankin score in the right knee of the KHC rabbits was significantly larger than that of JW rabbits (23.0±1.8 and 15.2±4.8, respectively, p < 0.01). Mean Mankin score in the left knee (Sham op. side) of the KHC rabbits was also significantly larger than that of JW rabbits (6.5±1.4 and 2.5±2.0, respectively, p<0.05). Presence of ox-LDL and expression of LOX-1 were noted in the right knee cartilage of both rabbits. However, immunoreactivity of ox-LDL was stronger in the left knee of KHC rabbits than in that of JW rabbits. Immunoreactivity of bFGF in both right and left knee cartilages was significantly less in the KHW rabbits than in JW rabbits. In rabbit chondrocyte culture, ox-LDL significantly reduced bFGF mRNA expression in a dose dependent manner, and pretreatment with anti-LOX-1 monoclonal antibody (JTX92) significantly reversed this reduction.【Conclusion】 These observations support the hypothesis that hyperlipidemia may be one of risk factors for osteoarthritis and suggest that the ox-LDL/LOX-1 system may be involved. Reduction of bFGF expression in chondrocytes due to the system may cause the acceleration of cartilage degeneration. Less