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Title: Decorin binds myostatin and modulates its activity to muscle cells

Abstract

Myostatin, a member of TGF-{beta} superfamily of growth factors, acts as a negative regulator of skeletal muscle mass. The mechanism whereby myostatin controls the proliferation and differentiation of myogenic cells is mostly clarified. However, the regulation of myostatin activity to myogenic cells after its secretion in the extracellular matrix (ECM) is still unknown. Decorin, a small leucine-rich proteoglycan, binds TGF-{beta} and regulates its activity in the ECM. Thus, we hypothesized that decorin could also bind to myostatin and participate in modulation of its activity to myogenic cells. In order to test the hypothesis, we investigated the interaction between myostatin and decorin by surface plasmon assay. Decorin interacted with mature myostatin in the presence of concentrations of Zn{sup 2+} greater than 10 {mu}M, but not in the absence of Zn{sup 2+}. Kinetic analysis with a 1:1 binding model resulted in dissociation constants (K {sub D}) of 2.02 x 10{sup -8} M and 9.36 x 10{sup -9} M for decorin and the core protein of decorin, respectively. Removal of the glycosaminoglycan chain by chondroitinase ABC digestion did not affect binding, suggesting that decorin could bind to myostatin with its core protein. Furthermore, we demonstrated that immobilized decorin could rescue the inhibitory effectmore » of myostatin on myoblast proliferation in vitro. These results suggest that decorin could trap myostatin and modulate its activity to myogenic cells in the ECM.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [2];  [2];  [3]
  1. Meat Science Laboratory, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589 (Japan)
  2. Animal Genomics, AgResearch, Hamilton 2015 (New Zealand)
  3. Meat Science Laboratory, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589 (Japan). E-mail: nishi@anim.agr.hokudai.ac.jp
Publication Date:
OSTI Identifier:
20798799
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 340; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.12.060; PII: S0006-291X(05)02807-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; DIGESTION; GROWTH FACTORS; HYPOTHESIS; IN VITRO; LEUCINE; MODULATION; MUSCLES; SECRETION; ZINC IONS

Citation Formats

Miura, Takayuki, Kishioka, Yasuhiro, Wakamatsu, Jun-ichi, Hattori, Akihito, Hennebry, Alex, Berry, Carole J., Sharma, Mridula, Kambadur, Ravi, and Nishimura, Takanori. Decorin binds myostatin and modulates its activity to muscle cells. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.12.060.
Miura, Takayuki, Kishioka, Yasuhiro, Wakamatsu, Jun-ichi, Hattori, Akihito, Hennebry, Alex, Berry, Carole J., Sharma, Mridula, Kambadur, Ravi, & Nishimura, Takanori. Decorin binds myostatin and modulates its activity to muscle cells. United States. doi:10.1016/j.bbrc.2005.12.060.
Miura, Takayuki, Kishioka, Yasuhiro, Wakamatsu, Jun-ichi, Hattori, Akihito, Hennebry, Alex, Berry, Carole J., Sharma, Mridula, Kambadur, Ravi, and Nishimura, Takanori. Fri . "Decorin binds myostatin and modulates its activity to muscle cells". United States. doi:10.1016/j.bbrc.2005.12.060.
@article{osti_20798799,
title = {Decorin binds myostatin and modulates its activity to muscle cells},
author = {Miura, Takayuki and Kishioka, Yasuhiro and Wakamatsu, Jun-ichi and Hattori, Akihito and Hennebry, Alex and Berry, Carole J. and Sharma, Mridula and Kambadur, Ravi and Nishimura, Takanori},
abstractNote = {Myostatin, a member of TGF-{beta} superfamily of growth factors, acts as a negative regulator of skeletal muscle mass. The mechanism whereby myostatin controls the proliferation and differentiation of myogenic cells is mostly clarified. However, the regulation of myostatin activity to myogenic cells after its secretion in the extracellular matrix (ECM) is still unknown. Decorin, a small leucine-rich proteoglycan, binds TGF-{beta} and regulates its activity in the ECM. Thus, we hypothesized that decorin could also bind to myostatin and participate in modulation of its activity to myogenic cells. In order to test the hypothesis, we investigated the interaction between myostatin and decorin by surface plasmon assay. Decorin interacted with mature myostatin in the presence of concentrations of Zn{sup 2+} greater than 10 {mu}M, but not in the absence of Zn{sup 2+}. Kinetic analysis with a 1:1 binding model resulted in dissociation constants (K {sub D}) of 2.02 x 10{sup -8} M and 9.36 x 10{sup -9} M for decorin and the core protein of decorin, respectively. Removal of the glycosaminoglycan chain by chondroitinase ABC digestion did not affect binding, suggesting that decorin could bind to myostatin with its core protein. Furthermore, we demonstrated that immobilized decorin could rescue the inhibitory effect of myostatin on myoblast proliferation in vitro. These results suggest that decorin could trap myostatin and modulate its activity to myogenic cells in the ECM.},
doi = {10.1016/j.bbrc.2005.12.060},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 340,
place = {United States},
year = {Fri Feb 10 00:00:00 EST 2006},
month = {Fri Feb 10 00:00:00 EST 2006}
}