Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: implications for cartilage destruction and repair

Arthritis Rheum. 2006 Feb;54(2):540-50. doi: 10.1002/art.21574.


Objective: To identify the genes up-regulated by interleukin-1 (IL-1) in combination with oncostatin M (OSM) in chondrocytes that may be involved in mechanisms of cartilage repair and degradation.

Methods: Gene microarray and real-time polymerase chain reaction (PCR) experiments were performed using RNA from SW1353 chondrocytes and primary human articular chondrocytes. Sections prepared from murine joints, injected with adenovirus vectors overexpressing IL-1 and/or OSM, were analyzed by immunohistochemistry for selected proteins.

Results: The combination of IL-1 and OSM markedly up-regulated the expression of various genes, including matrix metalloproteinases (MMPs), cytokines, chemokines, extracellular matrix components, and genes involved in signal transduction. Real-time PCR confirmed a synergistic induction of several MMPs, activin A, pentraxin 3 (PTX-3), and IL-8. The in vivo findings further indicated that stimulation with IL-1 plus OSM induced protein expression of activin A, PTX-3, and KC (the murine homolog of IL-8), as compared with the changes induced by individual cytokine treatment and unstimulated controls.

Conclusion: The results confirm that the potent proinflammatory cytokine combination of IL-1 plus OSM synergistically and coordinately up-regulates many genes and several MMPs. Moreover, chondrocytes exhibit a potential repair response following this procatabolic stimulus such that the repair mechanisms are ultimately overwhelmed by degradative processes in the cartilage. This gene-profiling study provides insight into the complex processes that mediate joint disease in the inflammatory arthritides through the coordinated expression of multiple genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / pathology
  • Chondrogenesis / drug effects*
  • Chondrogenesis / genetics
  • Cytokines / pharmacology*
  • Drug Combinations
  • Drug Synergism
  • Humans
  • Inflammation Mediators / pharmacology*
  • Interleukin-1 / pharmacology*
  • Oligonucleotide Array Sequence Analysis
  • Oncostatin M
  • RNA, Messenger / analysis
  • Up-Regulation / drug effects*
  • Up-Regulation / genetics


  • Cytokines
  • Drug Combinations
  • Inflammation Mediators
  • Interleukin-1
  • OSM protein, human
  • RNA, Messenger
  • Oncostatin M