FIBROBLAST GROWTH-FACTOR ENHANCES EXPRESSION OF TGF-BETA-STIMULATED-CLONE-22 GENE IN OSTEOBLAST-LIKE CELLS

Transforming growth factor-beta 1 (TGF beta 1)-stimulated clone 22 (TSC-22) is a primary response gene isolated by subtractive screening of genes expressed in murine osteoblastic cells treated with TGF beta 1, which is one of the cytokines abundantly stored in bone. Fibroblast growth factor (FGF) is also stored in bone matrix and acts as a potent autocrine/paracrine modulator of osteoblastic function. In this report, we investigated FGF effects on the expression of TSC-22 gene in a murine osteoblast-like cell line, MC3T3E-1. Treatment with recombinant basic FGF enhanced TSC-22 mRNA level in these cells within 1 h. This effect peaked at 2 h with several fold enhancement, after which the mRNA abundance returned to the basal level by 24 h. The FGF effect was dose-dependent, starting at 0.2 ng/ml, peaking at 2 ng/ml, and then declining at 20 ng/ml. The FGF effect on TSC-22 mRNA was blocked by actinomycin D, indicating the involvement of transcriptional events. The FGF enhancement of TSC-22 mRNA expression was partially blocked by genistein. Additive effect was observed upon cotreatment with saturating concentrations of FGF and TGF beta, suggesting the presence of at least two independent pathways for the two cytokines in the regulation of TSC-22 gene expression. These results indicate that the TSC-22 gene is one of the targets of FGF action in osteoblasts.