Osteopontin deficiency delays inflammatory infiltration and the onset of muscle regeneration in a model of muscle injury

Osteopontin is secreted by skeletal muscle myoblasts and stimulates their proliferation. Expression of osteopontin in skeletal muscle is up-regulated in pathological conditions including Duchenne muscular dystrophy, and recent evidence suggests that osteopontin may influence the course of this disease. The current study was undertaken to determine whether osteopontin regulates skeletal muscle regeneration, using a whole muscle autografting model of regeneration in osteopontin-null and wildtype mice. Osteopontin expression was found to be strongly up-regulated in wildtype grafts during the initial degeneration and subsequent early regeneration phases that are observed in this model. Grafted muscles from osteopontin-null mice degenerated more slowly than those of wildtype mice, as determined by histological assessment, fibre diameter and fibre number. The delayed degeneration in osteopontin-null grafts was associated with a delay in neutrophil and macrophage infiltration. Centrally nucleated (regenerating) muscle fibres also appeared more slowly in osteopontin-null grafts than in wildtype grafts. These results demonstrate that osteopontin plays a non-redundant role in muscle remodelling following injury.