Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta

Significance Osteogenesis imperfecta (brittle bone disease) is an incurable genetic disorder. We demonstrate that maternal deficiency of myostatin (a negative regulator of muscle growth) can enhance bone biomechanical strength and integrity in control and osteogenesis imperfecta mouse offspring, using three independent approaches. We provide evidence that bone is responsive to developmental programming and that myostatin can mediate these effects. Embryo transfer experiments show that the effects of maternal myostatin deficiency are conferred by the postimplantation environment. These studies represent a paradigm shift in understanding and treating osteogenesis imperfecta—a shift from believing only genetic and postnatal environmental factors control bone health to the inclusion of prenatal/perinatal developmental programming as a modifiable factor controlling adult bone health.