Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration

Skelet Muscle. 2016 Oct 4;6:34. doi: 10.1186/s13395-016-0104-8. eCollection 2016.

Abstract

Background: The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells.

Results: Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche.

Conclusions: Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

Keywords: Cell adhesion; Cell migration; Muscle regeneration; Muscular dystrophy; Niche; Pax7; Satellite cells; Syndecan-3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Homeostasis*
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiology*
  • Regeneration*
  • Satellite Cells, Skeletal Muscle / pathology
  • Satellite Cells, Skeletal Muscle / physiology*
  • Stem Cell Niche*
  • Syndecan-3 / genetics
  • Syndecan-3 / physiology*

Substances

  • Sdc3 protein, mouse
  • Syndecan-3