Youngjae Jeong1, Salah A Daghlas1, Alp S Kahveci1, Daniel Salamango1, Bettina A Gentry2, Marybeth Brown3, R Scott Rector4, R Scott Pearsall5, Charlotte L Phillips1. 1. Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, Missouri, 65211, USA. 2. Department of Veterinary Pathology, University of Missouri, Columbia, Missouri, USA. 3. Biomedical Science and Physical Therapy Program, University of Missouri, Columbia, Missouri, USA. 4. Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA. 5. Acceleron Pharma, Inc., Cambridge, Massachusetts, USA.
Abstract
INTRODUCTION: Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfecta murine (oim) and +/G610C. METHODS: Wild-type (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 with 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. Muscle Nerve 57: 294-304, 2018.
INTRODUCTION:Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfectamurine (oim) and +/G610C. METHODS: Wild-type (WT), +/G610C, and oim/oimmice 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/oimmice had increased hindlimb muscle weights and myofiber cross-sectional area compared with vehicle-treated counterparts. sActRIIB-mFc-treated oim/oimmice 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/oimmice. ActRIIB inhibitors may provide a potential mutation-specific therapeutic option for compromised muscle function in OI. Muscle Nerve 57: 294-304, 2018.
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