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

Osteoarthritis Cartilage. 2007 Mar;15(3):281-90. doi: 10.1016/j.joca.2006.07.010. Epub 2006 Aug 30.


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 (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.

Results: There 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.

Conclusion: The ox-LDL/LOX-1 system may be involved in human OA.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Lipoproteins, LDL / metabolism*
  • Male
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Proteoglycans / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Scavenger Receptors, Class E / metabolism*


  • Lipoproteins, LDL
  • Proteoglycans
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein