Osteopontin deficiency delays inflammatory infiltration and the onset of muscle regeneration in a mouse model of muscle injury.
Osteopontin is secreted by skeletal muscle myoblasts and stimulates their proliferation. Expression of osteopontin in skeletal muscle is upregulated in pathological conditions including Duchenne muscular dystrophy, and recent evidence suggests that osteopontin might influence the course of this disease. The current study was undertaken to determine whether osteopontin regulates skeletal muscle regeneration. A whole muscle autografting model of regeneration in osteopontin-null and wild-type mice was used. Osteopontin expression was found to be strongly upregulated in wild-type grafts during the initial degeneration and subsequent early regeneration phases that are observed in this model. Grafted muscle from osteopontin-null mice degenerated more slowly than that of wild-type 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 wild-type grafts. These results demonstrate that osteopontin plays a non-redundant role in muscle remodelling following injury.
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia.
Kitipong
K
Uaesoontrachoon
Dimuthu K
DK
Wasgewatte Wijesinghe
Eleanor J
EJ
Mackie
Charles N
CN
Pagel
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000502:physiology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D032448:Myoblasts, Skeletal / Q000473:pathology / Q000502:physiology; D020556:Neutrophil Infiltration; D053495:Osteopontin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D014182:Transplantation, Autologous; D015854:Up-Regulation
C506896:Spp1 protein, mouse; D053495:Osteopontin