The interleukin-1 receptor in normal and osteoarthritic human articular chondrocytes. Identification as the type I receptor and analysis of binding kinetics and biologic function

Arthritis Rheum. 1992 May;35(5):530-40. doi: 10.1002/art.1780350507.


Objective: To identify and investigate the kinetic binding properties of interleukin-1 receptors (IL-1R), and examine the abilities of the 2 IL-1 isoforms to stimulate metalloprotease synthesis, in normal and osteoarthritic (OA) chondrocytes.

Methods: Receptor affinity and density were determined using radioligand binding experiments and flow cytometry. Immunocytochemical analysis and affinity cross-linking studies were performed for characterization of IL-1R.

Results: While no difference in receptor affinity between normal and OA chondrocytes was noted in binding studies (Kd approximately 30 pM), a 2-fold increase in receptor density was found in OA chondrocytes as compared with normal chondrocytes (mean 4,069 sites/cell versus 2,315 sites/cell). Flow cytometry experiments also showed a significant increase in receptor density in OA cells, as well as an enhancement in the percentage of positive cells in diseased cartilage compared with normal. Binding data for both IL-1 isoforms revealed a single class of binding sites and receptor specificity. Factors such as IL-2, interferon-gamma, tumor necrosis factor alpha, and bovine insulin did not compete with IL-1 beta. By covalent ligand cross-linking and electrophoretic analysis, only type I IL-1R, a protein of 80 kd, was detected on chondrocytes. By immunocytochemical analysis, IL-1R was identified at the cell membrane level, in both normal and OA chondrocytes. The presence of nuclear staining was also observed, but only in OA chondrocytes. Recombinant human IL-1 (alpha and beta) induced the secretion of stromelysin and collagenase in a dose-dependent manner. The IL-1 concentration required for half-maximal metalloprotease stimulation was 3-4 times lower in OA chondrocytes than in normal cells.

Conclusion: These results indicate that OA chondrocytes have a higher sensitivity to the stimulation of metalloprotease synthesis by IL-1 than do normal cells. This could be related to the increased levels of IL-1R expressed in the OA cells. The implications of these findings with regard to the possible roles of IL-1 and IL-1R in the pathogenesis of OA are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cartilage, Articular / ultrastructure*
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Middle Aged
  • Molecular Weight
  • Osteoarthritis / pathology*
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / chemistry
  • Receptors, Interleukin-1


  • Receptors, Immunologic
  • Receptors, Interleukin-1