Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function.

Introduction: Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. We investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in two distinct mouse models of OI, osteogenesis imperfecta murine (oim) and +/G610C mouse. Methods: Wildtype (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with Tris-Buffered Saline (vehicle) or sActRIIB-mFc and their hindlimb muscles evaluated for mass, morphology and contractile function. Results: sActRIIB-mFc-treated WT, +/G610C and oim/oim mice had increased hindlimb muscle weights and myofiber cross-sectional area compared to vehicle-treated counterparts. sActRIIB-mFc treated oim/oim mice also exhibited increased contractile function relative to vehicle treated counterparts. Discussion: Blocking endogenous ActRIIB was effective at increasing muscle size in mouse models of OI, and increasing contractile function in oim/oim mice. ActRIIB inhibitors may provide a potential mutation specific therapeutic option for compromised muscle function in OI. This article is protected by copyright. All rights reserved.