Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO = 0.60 +/- 0.11, control= 1.07 +/- 0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-beta 1 (rhEPO = 0.95 +/- 0.14, control= 1.05 +/- 0.16) and TNF-alpha (rhEPO = 0.73 +/- 0.20, control= 1.01 +/- 0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.