...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta
【24h】

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

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

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相关主题

摘要

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 (Mstn(tm1Sjl/+)) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn(tm1Sjl/+) 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 (Col1a2(oim)), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2(oim/+) offspring from natural mating of Mstn(tm1Sjl/+) dams to Col1a2(oim/+) 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 Col1a2(oim/+) dams to Col1a2(oim/+) sires. Finally, increased bone biomechanical strength of Col1a2(oim/+) offspring that had been transferred into Mstn(tm1Sjl/+) 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.

著录项

获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号