Identification of decorin derived peptides with a zinc dependent anti-myostatin activity

Neuromuscul Disord. 2012 Dec;22(12):1057-68. doi: 10.1016/j.nmd.2012.07.002. Epub 2012 Jul 31.


Decorin is a member of the small leucine-rich proteoglycan family and it is a component of the extracellular matrix. Decorin was previously shown to bind different molecules, including myostatin, in a zinc-dependent manner. Here, we investigated in detail the anti-myostatin activity of decorin and fragments thereof. We show that this protein displays in vitro anti-myostatin activities with an IC(50) of 2.3 × 10(-8)M. After intramuscular injection of decorin in dystrophic mdx and γ-sarcoglycan(-/-) mice, we observed a significant increase of the muscle mass and this effect was maximal 18 days after administration. Further, we show that the myostatin-binding site is located in the N-terminal domain of decorin. In fact, a peptide encompassing the 31-71 sequence retains full myostatin binding capacity and intramuscular injection of the peptide induces muscle hypertrophy. The evaluation of three additional peptides suggests a crucial role of the four cysteines within the conserved CX3CXCX6C motif of class I of the small leucine-rich proteoglycans. Altogether, our results show that the N-terminal domain of decorin is sufficient for the binding to myostatin and they underscore the crucial role for this interaction of zinc and the cysteine cluster.

MeSH terms

  • Animals
  • Decorin / metabolism
  • Decorin / pharmacology*
  • Extracellular Matrix Proteins / metabolism
  • Mice
  • Mice, Inbred mdx
  • Mice, Knockout
  • Muscle, Skeletal / drug effects
  • Muscular Diseases / drug therapy*
  • Myostatin / antagonists & inhibitors*
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Protein Binding / physiology
  • Proteoglycans / pharmacology
  • Zinc / metabolism*


  • Decorin
  • Extracellular Matrix Proteins
  • Myostatin
  • Peptides
  • Proteoglycans
  • Zinc