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Article
The pattern recognition receptor CD36 is a chondrocyte hypertrophy marker associated with suppression of catabolic responses and promotion of repair responses to inflammatory stimuli
Journal of Immunology
  • Denise L. Cecil, VA San Diego Healthcare System
  • C. Thomas G. Appleton, Western University
  • Monika D. Polewski, VA San Diego Healthcare System
  • John S. Mort, McGill University
  • Ann Marie Schmidt, Columbia University in the City of New York
  • Alison Bendele, University of Colorado Boulder
  • Frank Beier, Western University
  • Robert Terkeltaub, VA San Diego Healthcare System
Document Type
Article
Publication Date
4-15-2009
URL with Digital Object Identifier
10.4049/jimmunol.0803603
Abstract

Multiple inflammatory mediators in osteoarthritis (OA) cartilage, including S100/calgranulin ligands of receptor for advanced glycation end products (RAGE), promote chondrocyte hypertrophy, a differentiation state associated with matrix catabolism. In this study, we observed that RAGE knockout was not chondroprotective in instability-induced knee OA in 8-wk-old mice. Hence, we tested the hypothesis that expression of the alternative S100/calgranulin and patterning receptor CD36, identified here as a marker of growth plate chondrocyte hypertrophy, mediates chondrocyte inflammatory and differentiation responses that promote OA. In rat knee joint destabilization-induced OA, RAGE expression was initially sparse throughout cartilage but increased diffusely by 4 wk after surgery. In contrast, CD36 expression focally increased at sites of cartilage injury and colocalized with developing chondrocyte hypertrophy and aggrecan cleavage NITEGE neoepitope formation. However, CD36 transfection in normal human knee-immortalized chondrocytes (CH-8 cells) was associated with decreased capacity of S100A11 and TNF-α to induce chondrocyte hypertrophy and ADAMTS-4 and matrix metalloproteinase 13 expression. S100A11 lost the capacity to inhibit proteoglycans synthesis and gained the capacity to induce proteoglycan synthesis in CD36-transfected CH-8 cells. Moreover, S100A11 required the p38 MAPK pathway kinase MKK3 to induce NITEGE development in mouse articular cartilage explants. However, CH-8 cells transfected with CD36 demonstrated decreased S100A11-induced MKK3 and p38 phosphorylation. Therefore, RAGE and CD36 patterning receptor expression were linked with opposing effects on inflammatory, procatabolic responses to S100A11 and TNF-α in chondrocytes.

Notes

This article is freely available from the journal

Citation Information
Denise L. Cecil, C. Thomas G. Appleton, Monika D. Polewski, John S. Mort, et al.. "The pattern recognition receptor CD36 is a chondrocyte hypertrophy marker associated with suppression of catabolic responses and promotion of repair responses to inflammatory stimuli" Journal of Immunology (2009) p. 5024 - 5031
Available at: http://works.bepress.com/frank-beier/51/