SYNDECAN-1 EXPRESSION INHIBITS MYOBLAST DIFFERENTIATION THROUGH A BASIC FIBROBLAST GROWTH FACTOR-DEPENDENT MECHANISM

Expression of syndecan-1, a cell-surface heparan sulfate proteoglycan, is down-regulated during skeletal muscle differentiation (Larrain, J. , Cizmeci-Smith, G,, Troncoso, V., Stahl, R, C,, Carey, D, J,, and Bra ndan, E. (1997) J. Biol. Chem, 272, 18418-18424). We examined the role of syndecan-1 in basic fibroblast growth factor (bFGF)-dependent inhi bition of myogenesis. C2C12 myoblasts were stably transfected with an expression plasmid containing the rat syndecan-1 coding region cDNA. C onstitutive syndecan-1 expression resulted in a strongly diminished ca pacity of the transfected clones to differentiate and to express skele tal muscle-specific markers such as fusion, creatine kinase, and myosi n. The expression of myogenin, a master transcription factor for muscl e differentiation, was also reduced and delayed. Analysis of the induc tion of a myogenin promoter-driven reporter revealed that syndecan-1 e xpression resulted in a 6-7-fold increase in sensitivity to bFGF-depen dent inhibition of myogenin expression. Transfecting the cells with a plasmid containing myogenin cDNA reversed the inhibition of myogenin t ranscriptional activation and myosin expression in syndecan-1-transfec ted cells; however, cell fusion was not observed. These results demons trate that syndecan-1 expression enhances cell responsiveness to bFGF and inhibits myoblast fusion and suggest that muscle terminal differen tiation is regulated by syndecan-1 expression.