2010 Fiscal Year Final Research Report

Regulation of skeletal muscles by RNA interference for Myostatin

Research Project

Project/Area Number	21792079
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Orthodontic/Pediatric dentistry
Research Institution	The University of Tokushima
Principal Investigator	KINOUCHI Nao The University of Tokushima, 病院, 助教 (30457329)
Project Period (FY)	2009 – 2010
Keywords	歯科矯正学
Research Abstract	In this study, we examined whether systemic administration of the myostatin-siRNA /ATCOL (Mst-siRNA / ATCOL) complex effectively silenced myostatin expression in caveolin-3-deficient mouse model of limb-girdle muscular dystrophy 1C(LGMDIC) mice. We observed the enlargement of a number of skeletal muscles, and more in mice treated with Mst-siRNA /ATCOL muscles than control. Moreover, the average myofibril size for Mst-siRNA / ATCOL-treated muscle was increased by approximately 1. 2-fold relative to control. We evaluated the contractile properties of Mst-siRNA / ATCOL-treated LGMDIC muscle. Hypertrophied Mst-siRNA-positive LGMDIC fibers seemed to improve contractile force generation. Notably, the level of contractile force was improved by approximately 60% in Mst-siRNA / ATCOL-treated wild type muscles relative to control. These results provide evidence that ATCOL-mediated systemic administration of siRNAs may be a powerful therapeutic tool for muscular atrophy.