Retinoic acid induces adult muscle cell differentiation mediated by the retinoic acid receptor-α

✍ Scribed by Orna Halevy; Orna Lerman

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 802 KB
• Volume: 154
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041540315

✦ Synopsis

Retinoic acid (RA) is known to induce differentiation in many ccll systems. This induction is mediated by nuclear RA receptors (RARs), which act as transactivating factors belonging to the superfamily of steroidithyroid nuclear receptors. In this study, effects of RA were studied in a mouse myogenic C2 cell line and in primary chicken satellite cells, the rnyogenic precursor cells in adult muscle. Addition of RA decreased thc rate of DNA synthesis in a dose-dependent manner in both cultures. Differentiation was more rapid in cells treated with RA, and these cells exhibited large myotubes after 48 hr of incubation as compared to untreated cells, which were still proliferating. Addition of l o p 8 M RA to C2 cells elevated mKNA levels of myogenin, a skeletal muscle-specific transcription factor. In parallel, activity levels of the muscle-specific creatine kinase were cnhanced in the RA-treated cells nearly twofold as compared to the untreated cells. RA treatment of both mouse CZ and chicken satellite cells caused rapid induction of the RAR-a rnRNA levels. Maximal mRNA lcvels were observed after 2 to 5 hr followed by a sharp reduction to nearly zero lev& at 9 hr. The KAR-a mRNA levels augmented in a dose-dependent manner between concentrations of lo-'" M and 10 M RA, whercas higher concentration5 caused mRNA levels to decrease. These results indicate that RA induccs differentiation in both adult skeletal muscle primary satellite cells and a niyogenic cell line. The rapid and specific induction of RAR-a rnRNA in these cells upon exposure to RA may suggest that this receptor is the primary target and a mediator of RA. GJ 1993 WiIev-Liss, Iiir.