Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes

J Clin Invest. 1994 Dec;94(6):2307-16. doi: 10.1172/JCI117595.


Immortalized human chondrocytes were established by transfection of primary cultures of juvenile costal chondrocytes with vectors encoding simian virus 40 large T antigen and selection in suspension culture over agarose. Stable cell lines were generated that exhibited chondrocyte morphology, continuous proliferative capacity (> 80 passages) in monolayer culture in serum-containing medium, and expression of mRNAs encoding chondrocyte-specific collagens II, IX, and XI and proteoglycans in an insulin-containing serum substitute. They did not express type X collagen or versican mRNA. These cells synthesized and secreted extracellular matrix molecules that were reactive with monoclonal antibodies against type II collagen, large proteoglycan (PG-H, aggrecan), and chondroitin-4- and chondroitin-6-sulfate. Interleukin-1 beta (IL-1 beta) decreased the levels of type II collagen mRNA and increased the levels of mRNAs for collagenase, stromelysin, and immediate early genes (egr-1, c-fos, c-jun, and jun-B). These cell lines also expressed reporter gene constructs containing regulatory sequences (-577/+3,428 bp) of the type II collagen gene (COL2A1) in transient transfection experiments, and IL-1 beta suppressed this expression by 50-80%. These results show that immortalized human chondrocytes displaying cartilage-specific modulation by IL-1 beta can be used as a model for studying normal and pathological repair mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Viral, Tumor / isolation & purification
  • Cartilage / cytology
  • Cartilage / drug effects
  • Cartilage / physiology*
  • Cell Line / drug effects
  • Cell Line / physiology*
  • Cell Transformation, Viral
  • Chondroitin Sulfates / isolation & purification
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Cycloheximide / pharmacology
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology*
  • Phenotype
  • Proteoglycans / isolation & purification
  • RNA, Messenger / analysis
  • Ribs / cytology
  • Ribs / physiology
  • Simian virus 40 / genetics


  • Antigens, Viral, Tumor
  • Interleukin-1
  • Proteoglycans
  • RNA, Messenger
  • Chondroitin Sulfates
  • Collagen
  • Cycloheximide