Expression of N-cadherin, N-CAM, fibronectin and tenascin is stimulated by TGF- beta 1, beta 2, beta 3 and beta 5 during the formation of precartilage condensations

Cell surface adhesion and extracellular matrix proteins are known to play a key role in the formation of cell condensations during skeletal development, and their formation is crucial for the expression of cartilage-specific genes. However, little is known about the relationship between adhesion molecules (N-cadherin and N-CAM), extracellular matrix proteins (fibronectin and tenascin) and TGF- beta 1, TGF- beta 2 and TGF- beta 3 during in vitro precartilage condensations in mouse chondrogenesis. On these bases, we determined the participation of mammalian TGF- beta 1, TGF- beta 2 and TFG- beta 3 and Xenopus TGF- beta 5 on the expression of cell surface adhesion and extracellular matrix proteins during the formation of precartilage condensations. Also, we characterized the effects of TGF- beta s on proteoglycan metabolism at different cellular densities in mouse embryonic limb bud mesenchymal cells. In TGF- beta 1 and TGF- beta 5-treated cultures, proteoglycan biosynthesis was higher than in controls, while there were no differences in proteoglycan catabolism, which caused the accumulation of cartilage extracellular matrix. When mesenchymal cells were seeded at three different cellular densities in the presence of TGF- beta s, only high density cultures presented increased stimulation of proteoglycan biosynthesis, compared to low and intermediate densities. To determine whether the effect of TGF- beta s on precartilage condensations is mediated through the expression of N-cadherin, N-CAM, fibronectin and tenascin, we evaluated their expression. Results showed that TGF- beta 1, TGF- beta 2, TGF- beta 3, and TGF- beta 5 differentially enhanced the expression of N-cadherin, N-CAM, fibronectin and tenascin in precartilage condensations, suggesting that TGF- beta isoforms play an important role in the establishment of cell-cell and cell-extracellular matrix interactions during precartilage condensations.