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

Arin K. Oestreich, William M. Kamp, Marcus G. McCray, Stephanie M. Carleton, Natalia Karasseva, Kristin L. Lenz, Youngjae Jeong, Salah A. Daghlas, Xiaomei Yao, Yong Wang, Ferris M. Pfeiffer, Mark R. Ellersieck, Laura C. Schulz, Charlotte L. Phillips

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstntm1Sjl/+) increases musclemass inwild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstntm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2oim), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2oim/+ offspring from natural mating of Mstntm1Sjl/+ dams to Col1a2oim/+sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2oim/+ dams to Col1a2oim/+ sires. Finally, increased bone biomechanical strength of Col1a2oim/+ offspring that had been transferred into Mstntm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

Original languageEnglish
Pages (from-to)13522-13527
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 22 2016


  • Bone health
  • Developmental origins of health and disease
  • Fetal programming
  • Myostatin
  • Osteogenesis imperfecta


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