Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin fragments in human articular chondrocytes

Osteoarthritis Cartilage. 2005 Oct;13(10):879-86. doi: 10.1016/j.joca.2005.04.017. Epub 2005 Jun 14.


Objective: The objective of this study was to examine expression and regulation of Toll-like receptor 2 (TLR2) in human articular chondrocytes.

Methods: Human articular chondrocytes were enzymatically isolated from normal and osteoarthritic knee cartilage. Immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the expression of toll-like receptors. Following stimulation of chondrocytes in vitro by IL-1beta and fibronectin proteolytic fragments, the relative levels of mRNA for TLR2 were determined by quantitative real-time PCR. MyD88 activation and nuclear factor-kappaB (NF-kappaB) translocation were evaluated by immunoprecipitation and electrophoretic mobility shift assay, respectively.

Results: Human articular chondrocytes mainly expressed TLR1, 2, 5 by RT-PCR. Protein expression of TLR2 was also identified in adult human articular cartilage. TLR2 was upregulated following IL-1beta and fibronectin proteolytic fragments stimulation in primary cultures of osteoarthritic articular chondrocytes. Fibronectin proteolytic fragments-induced TLR2 upregulation involved an IL-1beta autocrine/paracrine pathway.

Conclusions: TLR2 is expressed in human articular cartilage and is upregulated by proarthritic agents including IL-1beta and fibronectin fragments. Signaling through TLR is a novel pro-inflammatory mechanism in osteoarthritis and targeting of these signaling pathways may be of value in treatment of degenerative joint disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blotting, Western
  • Cartilage, Articular / immunology*
  • Cells, Cultured
  • Chondrocytes / immunology*
  • Fibronectins / immunology
  • Gene Expression Regulation
  • Humans
  • Interleukin-1 / immunology*
  • Middle Aged
  • Osteoarthritis, Knee / immunology*
  • Peptide Fragments / immunology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Signal Transduction / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism*


  • Fibronectins
  • Interleukin-1
  • Peptide Fragments
  • RNA, Messenger
  • Toll-Like Receptor 2