Research Article: Age dependent increase in the levels of osteopontin inhibits skeletal muscle regeneration

Date Published: August 15, 2012

Publisher: Impact Journals LLC

Author(s): Preeti Paliwal, Novalia Pishesha, Denny Wijaya, Irina M Conboy.

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Abstract

Skeletal muscle regeneration following injury is accompanied by rapid infiltration of macrophages, which play a positive role in muscle repair. Increased chronic inflammation inhibits the regeneration of dystrophic muscle, but the properties of inflammatory cells are not well understood in the context of normal muscle aging. This work uncovers pronounced age-specific changes in the expression of osteopontin (OPN) in CD11b+ macrophages present in the injured old muscle as well as in the blood serum of old injured mice and in the basement membrane surrounding old injured muscle fibers. Furthermore, young CD11b+ macrophages enhance regenerative capacity of old muscle stem cells even when old myofibers and old sera are present; and neutralization of OPN similarly rejuvenates the myogenic responses of old satellite cells in vitro and notably, in vivo. This study highlights potential mechanisms by which age related inflammatory responses become counter-productive for muscle regeneration and suggests new strategies for enhancing muscle repair in the old.

Partial Text

Skeletal muscle displays a robust regenerative response upon injury where muscle stem cells (satellite cells) exit quiescence, undergo activation, proliferation and fuse to form newly regenerating myofibers [1, 2]. This process is accompanied by inflammation, e.g. infiltration of immune cells, primarily macrophages, at the site of muscle injury [3]. While it has been shown that inflammation generally increases with aging, which has been attributed to impaired immune response [4-6], several previous studies have demonstrated that in the young animals inflammatory macrophages play a positive role in clearing the wound and promoting muscle regeneration [7-13].

Skeletal muscle injury is accompanied by rapid infiltration of immune cells, where macrophages play a prominent role in successful tissue regeneration [8, 12]. With age, the muscle environment dramatically changes and becomes unsupportive for the regenerative responses of satellite cells [5, 38, 39]. Multiple age-specific differences in the niche of satellite cells have been implicated in the decline of old muscle repair, however, relatively little is known about the role of altered inflammatory response in the aging of tissue regeneration either in general or in skeletal muscle.

 

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