气候变化领域集成服务门户(CCPortal): Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway

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DOI	10.1073/pnas.2111401118
	Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway
	Liu Y.; Lehar A.; Rydzik R.; Chandok H.; Lee Y.-S.; Youngstrom D.W.; George J.; Matzuk M.M.; Germain-Lee E.L.; Lee S.-J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	Skeletal muscle and bone homeostasis are regulated by members of the myostatin/GDF-11/activin branch of the transforming growth factor-β superfamily, which share many regulatory components, including inhibitory extracellular binding proteins and receptors that mediate signaling. Here, we present the results of genetic studies demonstrating a critical role for the binding protein follistatin (FST) in regulating both skeletal muscle and bone. Using an allelic series corresponding to varying expression levels of endogenous Fst, we show that FST acts in an exquisitely dose-dependent manner to regulate both muscle mass and bone density. Moreover, by employing a genetic strategy to target Fst expression only in the posterior (caudal) region of the animal, we show that the effects of Fst loss are mostly restricted to the posterior region, implying that locally produced FST plays a much more important role than circulating FST with respect to regulation of muscle and bone. Finally, we show that targeting receptors for these ligands specifically in osteoblasts leads to dramatic increases in bone mass, with trabecular bone volume fraction being increased by 12- to 13-fold and bone mineral density being increased by 8- to 9-fold in humeri, femurs, and lumbar vertebrae. These findings demonstrate that bone, like muscle, has an enormous inherent capacity for growth that is normally kept in check by this signaling system and suggest that the extent to which this regulatory mechanism may be used throughout the body to regulate tissue mass may be more significant than previously appreciated. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Activin; Bone mineral density; Chalone; Follistatin; Myostatin
语种	英语
scopus关键词	activin; chalone; follistatin; transforming growth factor beta; follistatin; transforming growth factor beta; adult; animal experiment; animal tissue; Article; bone density; bone mass; bone volume; controlled study; female; gene expression; gene loss; male; mouse; muscle mass; nonhuman; osteoblast; signal transduction; skeletal muscle; trabecular bone; allele; animal; bone development; gene expression regulation; genetics; growth, development and aging; heterozygote; homeostasis; metabolism; multigene family; physiology; signal transduction; skeletal muscle; Alleles; Animals; Bone Density; Bone Development; Follistatin; Gene Expression Regulation; Gene Expression Regulation, Developmental; Heterozygote; Homeostasis; Mice; Multigene Family; Muscle, Skeletal; Signal Transduction; Transforming Growth Factor beta
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251070
作者单位	The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, United States; Department of Orthopaedic Surgery, University of Connecticut, School of Medicine, Farmington, CT 06030, United States; Department of Molecular Genetics, Seoul National University, Seoul, 08826, South Korea; Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, South Korea; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, United States; Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030, United States; Department of Pediatrics, University of Connecticut, School of Medicine, Farmington, CT 06030, United States; Center for Regenerative Medicine and Skeletal Development, University of Connecticut, School of Dental Medicine, Farmington, CT 06030, United States; Division of Endocrinology, Center for Rare Bone Disorders, Connecticut Children's, Farmington, CT 06032, United States; Department of Genetics and Genome Sciences, Univers...
推荐引用方式 GB/T 7714	Liu Y.,Lehar A.,Rydzik R.,et al. Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway[J],2021,118(33).
APA	Liu Y..,Lehar A..,Rydzik R..,Chandok H..,Lee Y.-S..,...&Lee S.-J..(2021).Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Liu Y.,et al."Local versus systemic control of bone and skeletal muscle mass by components of the transforming growth factor-β signaling pathway".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).