SOLUBLE ACTIVIN RECEPTOR TYPE IIB DECOY RECEPTOR DIFFERENTIALLY IMPACTS MURINE OSTEOGENESIS IMPERFECTA MUSCLE FUNCTION

作者：Jeong Youngjae; Daghlas Salah A; Kahveci Alp S; Salamango Daniel; Gentry Bettina A; Brown Marybeth; Rector R Scott; Pearsall R Scott; Phillips Charlotte L^*

来源：Muscle & Nerve, 2018, 57(2): 294-304.

DOI：10.1002/mus.25706

• +/G610C
• activin receptor type IIB
• muscle
• myostatin
• osteogenesis imperfecta murine
• peak tetanic force

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 1/ G610C. Methods: Wild-type (WT), 1/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, 1/G610C, and oim/oim mice had increased hindlimb muscle weights and myofiber cross-sectional area compared with vehicle-treated counterparts. sActRIIB-mFctreated 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 mutationspecific therapeutic option for compromised muscle function in OI.

• 出版日期2018-2