| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3381807 | Osteoarthritis and Cartilage | 2007 | 10 Pages |
SummaryObjectiveUsing 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).MethodsThirty-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 (RT-PCR). Immunohistochemistry for ox-LDL and LOX-1 was performed in all samples. The histological OA 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 investigated by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and on proteoglycan synthesis by monitoring [35S] sulfate incorporation.ResultsThere was a statistically significant difference between mean LOX-1/GAPDH (LOX-1/human glyceraldehyde-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 (R2 = 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.ConclusionThe ox-LDL/LOX-1 system may be involved in human OA.
