FIBROBLAST-GROWTH-FACTOR DOWN-REGULATES EXPRESSION OF A BASIC HELIX-LOOP-HELIX-TYPE TRANSCRIPTION FACTOR, SCLERAXIS, IN A CHONDROCYTE-LIKE CELL-LINE, TC6

Scleraxis is a basic helix-loop-helix-type transcription factor that i s expressed in sclerotome. Fibroblast growth factor (FGF) is one of th e cytokines produced by the cells in skeletal tissues and is a potent modulator of skeletogenesis. The aim of this study was to examine the effects of FGF on the expression of scleraxis in chondrocyte-like cell s, TC6. In these cells, scleraxis mRNA was constitutively expressed as a 1.2 kb message at a high level in contrast to its low levels of exp ression in fibroblast-like cells or osteoblast-like cells. Upon treatm ent with FGF, scleraxis mRNA level was decreased within 12 h. This eff ect was at its nadir at 24 h and the scleraxis mRNA level returned to its base line level by 48 h. The FGF effect was maximal at 1 ng/ml. FC F effects on scleraxis were blocked by actinomycin D but not: by cyclo heximide, suggesting the involvement of transcriptional events that do not require new protein synthesis. The FGF effects on scleraxis were blocked by genistein, suggesting the involvement of tyrosine kinase in the post-receptor signaling. TGF beta treatment of TC6 cell is enhanc ed scleraxis mRNA expression; however, combination of the saturation c loses of FGF and TGF beta resulted in suppression of scleraxis mRNA le vel. BMP2 also suppressed scleraxis mRNA expression in TC6 cells and n o further suppression was observed in combination with FGF. These resu lts indicate that scleraxis is expressed in chondrocyte-like TC6 cells and it is one of the targets of FCF action in these cells. J. Cell. B iochem. 70:468-477. (C) 1998 Wiley-Liss, Inc.