Myoblasts are able to differentiate into other mesenchymal lineages including adipocytes and osteoblasts. However, it is not known how this differentiation is normally regulated in intact animals and humans. Here, we subjected cultured C2CI2 myoblasts to cyclic mechanical stretch (20% elongation) during differentiation into adipocytes. Mechanical stretch inhibited the myoblast-toadipocyte differentiation significantly, concurrent with an enhanced expression of WntlOb mRNA. Inhibition of the Writ signaling by incubation of the myoblasts with a soluble Writ ligand, sFRP-2, abolished the inhibitory function of mechanical stretch on adipogenesis. These findings provide evidence that mechanical stretch inhibits myoblast-to-adipocyte differentiation possibly through Writ signaling. (C) 2005 Elsevier Inc. All rights reserved.