Journal
FASEB JOURNAL
Volume 26, Issue 2, Pages 955-965Publisher
WILEY
DOI: 10.1096/fj.11-187575
Keywords
synaptogenesis; myogenesis; twitch force; acetylcholine receptors
Categories
Funding
- Center for Biomolecular and Tissue Engineering at Duke University
- U.S. National Institutes of Health from the National Institute of Arthritis and Musculoskeletal and Skin Disease [AR055226]
Ask authors/readers for more resources
Neural agrin plays a pleiotropic role in skeletal muscle innervation and maturation, but its specific effects on the contractile function of aneural engineered muscle remain unknown. In this study, neonatal rat skeletal myoblasts cultured within 3-dimensional engineered muscle tissue constructs were treated with 10 nM soluble recombinant miniagrin and assessed using histological, biochemical, and functional assays. Depending on the treatment duration and onset time relative to the stage of myogenic differentiation, miniagrin was found to induce up to 1.7-fold increase in twitch and tetanus force amplitude. This effect was associated with the 2.3-fold up-regulation of dystrophin gene expression at 6 d after agrin removal and enhanced ACh receptor (AChR) cluster formation, but no change in cell number, expression of muscle myosin, or important aspects of intracellular Ca2+ handling. In muscle constructs with endogenous ACh levels suppressed by the application of alpha-NETA, miniagrin increased AChR clustering and twitch force amplitude but failed to improve intracellular Ca2+ handling and increase tetanus-to-twitch ratio. Overall, our studies suggest that besides its synaptogenic function that could promote integration of engineered muscle constructs in vivo, neural agrin can directly promote the contractile function of aneural engineered muscle via mechanisms distinct from those involving endogenous ACh.-Bian, W., Bursac, N. Soluble miniagrin enhances contractile function of engineered skeletal muscle. FASEB J. 26, 955-965 (2012). www.fasebj.org
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available