Abstract
SUMMARYOsteopontin 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.
Highlights
Efficient regeneration of injured or dystrophic skeletal muscle relies upon the coordinated action of invading inflammatory cells that induce muscle fibre necrosis and phagocytosis (Lescaudron et al, 1999; Tidball and Wehling-Henricks, 2007), and an endogenous pool of quiescent myogenic stem cells known as satellite cells that form new muscle fibres (Zammit et al, 2006)
We have recently demonstrated that osteopontin is expressed by myoblasts in areas of focal muscle necrosis in the muscles of dystrophic mdx mice, and that recombinant mouse osteopontin is able to influence adhesion, proliferation and differentiation of skeletal muscle myoblasts (Uaesoontrachoon et al, 2008)
This study investigated the effect of acute osteopontin expression on the early stages of muscle regeneration, using whole muscle autografting of extensor digitorum longus muscles from either wild-type or osteopontin-null mice
Summary
Efficient regeneration of injured or dystrophic skeletal muscle relies upon the coordinated action of invading inflammatory cells that induce muscle fibre necrosis and phagocytosis (Lescaudron et al, 1999; Tidball and Wehling-Henricks, 2007), and an endogenous pool of quiescent myogenic stem cells known as satellite cells that form new muscle fibres (Zammit et al, 2006). Osteopontin, known as early T-lymphocyte activation 1 protein (ETA1), secreted phosphoprotein 1 (SPP1) and bone sialoprotein 1 (BSP1), is a member of the small integrin-binding N-linked glycoprotein family of proteins, which interacts with certain variants of the hyaluronan receptor CD44 and with a variety of integrins by both RGD-dependent and independent mechanisms (Denhardt and Guo, 1993). Osteopontin exists both as an adhesive component of the extracellular matrix and as a soluble molecule
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