Prevention of IGF-1 and TGF beta stimulated type II collagen and decorin expression by bFGF and identification of IGF-1 mRNA transcripts in articularchondrocytes

Objectives: The aim of this investigation was to establish whether the acti on of bFGF modulated the production of type II collagen, decorin and biglyc an induced by IGF-1 or TGF beta in porcine articular chondrocytes. In addit ion, the study would establish which multiple transcripts of IGF-I were pre sent in articular cartilage, and which growth factors influenced their expr ession. Methods: Steady state levels of mRNA specific for IGF-1 and matrix proteins were extracted as total RNA from porcine articular chondrocytes an d processed for Northern blot analysis. High-density cell monolayers were e stablished 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 TGF beta in the p resence or absence of bFGF. Results: bFGF prevented the stimulation of type II collagen and decorin induced in the presence of IGF-I or TGF beta and u p-regulated the production of biglycan in cultured chondrocytes without alt ering the gene expression of IGF-1. Four IGF-I transcripts were found in cu ltured adherent chondrocytes, approximately 77% was present as a major 4.7 kb transcript with lower levels of 7.6 (4%), 1.3 (11%) and 1.1 (8%) kb form s. Conclusions: bFGF acts as an antagonist for the production of type II co llagen and decorin and also acts as a strong inducer like IGF I and TGF bet a for the expression of biglycan in porcine cultured chondrocytes. The appa rent lack of a dose and time effect on expression of the IGF-1 gene was sur prising and may be due to the stability of the IGF-1 message. (C) 2001 Else vier Science B.V./International Society of Matrix Biology. All rights reser ved.