title: Fibrillin microfibrils in bone physiology.
abstract: The severe skeletal abnormalities associated with Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA) underscore the notion that fibrillin assemblies (microfibrils and elastic fibers) play a critical role in bone formation and function in spite of representing a low abundance component of skeletal matrices. Studies of MFS and CCA mice have correlated the skeletal phenotypes of these mutant animals with distinct pathophysiological mechanisms that reflect the contextual contribution of fibrillin-1 and -2 scaffolds to TGFβ and BMP signaling during bone patterning, growth and metabolism. Illustrative examples include the unique role of fibrillin-2 in regulating BMP-dependent limb patterning and the distinct impact of the two fibrillin proteins on the commitment and differentiation of marrow mesenchymal stem cells. Collectively, these findings have important implication for our understanding of the pathophysiological mechanisms that drive age- and injury-related processes of bone degeneration.
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Silvia
authors.initials: S
authors.lastname: Smaldone
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address: Francesco.ramirez@mssm.edu.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ramirez
mesh_terms: D000818:Animals; D054119:Arachnodactyly / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019521:Body Patterning; D002454:Cell Differentiation; D003286:Contracture / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D000071838:Fibrillin-1 / Q000235:genetics* / Q000378:metabolism; D000071840:Fibrillin-2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008382:Marfan Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D009154:Mutation; D010012:Osteogenesis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071840:Fibrillin-2; D016212:Transforming Growth Factor beta; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C000605728:Fbn2 protein, mouse
keywords: Autopod patterning; Bone marrow niche; Fibrillin; Marfan syndrome; Mesenchymal stem cells; Osteopenia; TGFβ and BMP signaling