Abstract
Differentiation of skeletal myoblasts in culture is negatively regulated by certain growth factors, including basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF beta). We investigated the effects of bFGF and TGF beta on D-type cyclin expression in skeletal myoblasts. When myoblasts were induced to differentiate in low mitogen medium, expression of cyclin D1 rapidly fell below detectable levels. In contrast, expression of cyclin D3 increased to levels exceeding those present in myoblasts. Expression of cyclin D1 was induced in myoblasts by bFGF and TGF beta (albeit with different kinetics for each factor), while induction of cyclin D3 expression was inhibited by these growth factors. Although these results are consistent with other reports showing induction of cyclin D1 by growth factors, induction of cyclin D3 expression during terminal differentiation of myoblasts and inhibition of this induction by growth factors is surprising. These results suggest that cyclin D3, previously thought to be only a positive regulator of cell cycle progression, may also function in the cellular context of terminal differentiated muscle. Stable expression of cyclin D1 from an ectopic viral promoter inhibits C2C12 myoblast differentiation, but only in those clones where the level of cyclin D1 expression does not significantly exceed that present in control myoblasts stimulated by bFGF. Together, these result suggest that cyclin D1 expression functions in the inhibition of myoblast differentiation by certain growth factors.
Highlights
Differentiation of skeletal myoblasts in culture is negatively regulated by certain growth factors, including basic fibroblast growth factor and transforming growth factor fJ (TGF{J)
We investigated the effects of basic fibroblast growth factor (bFGF) and TGFfJ on Dvtype cyclin expression in skeletal myoblasts
Expression of cyclin Dl was induced in myoblasts by bFGF and TGFfJ, while induction of cyclin D3 expression was inhibited by these growth factors
Summary
Vol 270, No., Issue of February 24, pp. 4093-4100, 1995 Printed in U.S.A. (Received for publication, August 5, 1994, and in revised form, November 18, 1994). A central issue in understanding the mechanism by which specific growth factors inhibit myoblast differentiation involves their specific effects on the activity of the myogenic basic helix-loop-helix (bHLH) regulators (reviewed by Weintraub et al (1991) and Olson (1992)). Loss of histone HI ph osphorylation at this epitope was shown to be directl y associate d wit h t he differentiation of myocytes rather than the acquisitio n of a qui escen t sta te by undifferen tia ted mononucl ear cells (Cole et al, 1993 ) Cyclins are t he regul atory subunit s of the cdk s, and th eir expression is modul ated a ccording to ty pe during cell cycle pr ogr ession. We show th at ectopic expression of cyclin Dl at levels equivalent to th ose expressed in cells stimula te d by bF GF inhibits differenti ation of C2C 12 myobl a s t s
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
