Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro

Osteoarthritis Cartilage. 2003 Nov;11(11):801-9. doi: 10.1016/s1063-4584(03)00168-7.


Objective: In normal articular cartilage cells, the IGFRI/insulin-like growth factor 1 (IGF-1) autocrine pathway was shown to overrule the catabolic effects of the IL-1/IL-1RI pathway by up-regulation of the IL-1RII decoy receptor. The activity of the IGF-1/IGFR1 and IL-1/IL-1R pathways, and of the IL-1RII control mechanism in the synthesis and turnover of the extracellular matrix (ECM) by chondrocytes from normal and osteoarthritic (OA) articular cartilage was compared in order to identify possible therapeutic targets of this disease.

Methods: Phenotypically stable human articular cartilage cells were obtained from normal and OA cartilage of the same knee showing focal OA. The cells were cultured in alginate beads over 1 week to re-establish the intracellular cytokine and growth factors, to reexpress the respective plasma membrane receptors and to reach equilibrium in accumulated cell-associated matrix (CAM) compounds. Following liberation of the cells from the alginate beads, the levels of cell-associated matrix (CAM) aggrecan, type II collagen and fibronectin, of intracellular IGF-1, IL-1alpha and beta and of their respective plasma membrane-bound receptors, IGFR1, IL-1RI and the decoy receptor IL-1RII, were assayed using flow cytometry.

Results: Coordinated production and accumulation of CAM aggrecan and type II collagen under the effect of the IGFR1/IGF-1 autocrine pathway-as documented for chondrocytes from healthy controls-was absent when the chondrocytes had been obtained from OA joints. When compared with cells obtained from normal tissues, chondrocytes from fibrillated OA cartilage expressed significantly higher intracellular IGF-1 levels and plasma membrane-bound IGFR1. At the same time, significantly higher intracellular IL-1alpha and beta levels and upregulated plasma membrane-bound IL-1RI were observed. Plasma membrane-bound IL-1RII decoy receptor was downregulated in OA chondrocytes. The levels of CAM aggrecan, type II collagen and fibronectin were significantly reduced in the chondrocytes obtained from pathological tissue.

Conclusion: Paired analysis of normal and OA chondrocytes from the same knee joint has shown an enhanced capacity of chondrocytes from OA cartilage to produce ECM macromolecules. However, the same cells have increased catabolic signalling pathways. As a consequence of this increased IL-1 activity and the reduced amounts of IL-1RII decoy receptor, less of the produced ECM macromolecules may persist in the CAM of the OA chondrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autocrine Communication
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cell Adhesion Molecules / metabolism
  • Cell Separation / methods
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Cytokines / metabolism
  • Extracellular Matrix / metabolism*
  • Female
  • Flow Cytometry / methods
  • Growth Substances / metabolism
  • Homeostasis*
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology
  • Paracrine Communication
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-1 Type I
  • Receptors, Interleukin-1 Type II


  • Cell Adhesion Molecules
  • Cytokines
  • Growth Substances
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Receptors, Interleukin-1 Type II
  • Receptor, IGF Type 1