Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-11, Vol.113 (47), p.13522-13527

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 muscle mass in wild-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.