Prevention of IGF-1 and TGFbeta stimulated type II collagen and decorin expression by bFGF and identification of IGF-1 mRNA transcripts in articular chondrocytes.

OBJECTIVES: the aim of this investigation was to establish whether the action of bFGF modulated the production of type II collagen, decorin and biglycan induced by IGF-1 or TGFbeta in porcine articular chondrocytes. In addition, the study would establish which multiple transcripts of IGF-1 were present in articular cartilage, and which growth factors influenced their expression.
METHODS: steady state levels of mRNA specific for IGF-1 and matrix proteins were extracted as total RNA from porcine articular chondrocytes and processed for Northern blot analysis. High-density cell monolayers were established in the presence of serum, then maintained in a serum-free state for up to 7 days with increasing doses of either IGF-1 or TGFbeta in the presence or absence of bFGF.
RESULTS: bFGF prevented the stimulation of type II collagen and decorin induced in the presence of IGF-1 or TGFbeta and up-regulated the production of biglycan in cultured chondrocytes without altering the gene expression of IGF-1. Four IGF-1 transcripts were found in cultured adherent chondrocytes, approximately 77% was present as a major 4.7kb transcript with lower levels of 7.6 (4%), 1.3 (11%) and 1.1 (8%) kb forms.
CONCLUSIONS: bFGF acts as an antagonist for the production of type II collagen and decorin and also acts as a strong inducer like IGF 1 and TGFbeta for the expression of biglycan in porcine cultured chondrocytes. The apparent lack of a dose and time effect on expression of the IGF-1 gene was surprising and may be due to the stability of the IGF-1 message.