MUSCLE SATELLITE CELLS FROM DYSTROPHIC (MDX) MICE HAVE ELEVATED LEVELS OF HEPARAN-SULFATE PROTEOGLYCAN RECEPTORS FOR FIBROBLAST GROWTH-FACTOR

Skeletal muscle has the remarkable capacity to regenerate new muscle f ibres in the event of injury or disease. This capacity lies in the sat ellite cells, which are myogenic stem cells residing in adult muscle. While the signals that activate satellite cells to divide in vivo are not fully understood, satellite cells grown in culture respond to the mitogenic action of fibroblast growth factor (FGF). Satellite cells fr om the dystrophic mdx mouse are more sensitive to FGF in culture than satellite cells from normal mice. In this study we investigated the ba sis for this heightened sensitivity of mdx satellite cells to FGF by m easuring the number and affinity of protein and heparan sulphate prote oglycan (HSPG) receptors for FGF. We found that HSPG receptors were el evated over four-fold in the mdx cells compared with cells from normal animals. We supported this observation by measuring the synthesis of heparan sulphate (HS) and chondroitin sulphate (CS) by satellite cells in culture. Mdx satellite cells synthesized approximately ten times m ore of these sulphated glycosaminoglycans (GAGs) than did normal cells . For muscle fibroblasts, however, we found no significant difference in the number or affinity of protein or HSPG receptors, or in the amou nt of sulphated GAGs synthesized, between normal and mdx cells. We pro pose that the increase in FGF HSPG receptors is the basis for the heig htened response of mdx satellite cells to FGF in culture and may refle ct exposure of the cells to growth factors in the degenerating mdx mus cle.