title: Material and mechanical properties of bones deficient for fibrillin-1 or fibrillin-2 microfibrils.
abstract: The contribution of non-collagenous components of the extracellular matrix to bone strength is largely undefined. Here we report that deficiency of fibrillin-1 or fibrillin-2 microfibrils causes distinct changes in bone material and mechanical properties. Morphometric examination of mice with hypomorphic or null mutations in fibrillin-1 or fibrillin-2, respectively, revealed appreciable differences in the postnatal shaping and growth of long bones. Fourier transform infrared imaging spectroscopy indicated that fibrillin-1 plays a predominantly greater role than fibrillin-2 in determining the material properties of bones. Biomechanical tests demonstrated that fibrillin-2 exerts a greater positive influence on the mechanical properties of bone than fibrillin-1 assemblies. Published evidence indirectly supports the notion that the above findings are mostly, if not exclusively, related to the differential control of TGFβ family signaling by fibrillin proteins. Our study therefore advances our understanding of the role that extracellular microfibrils play in bone physiology and implicitly, in the pathogenesis of bone loss in human diseases caused by mutations in fibrillin-1 or -2.
authors: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, NY 10029, USA.
authors: Emilio
authors: E
authors: Arteaga-Solis
authors: Lee
authors: L
authors: Sui-Arteaga
authors: Minwook
authors: M
authors: Kim
authors: Mitchell B
authors: MB
authors: Schaffler
authors: Karl J
authors: KJ
authors: Jepsen
authors: Nancy
authors: N
authors: Pleshko
authors: Francesco
authors: F
authors: Ramirez
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000235:genetics; D002254:Carbonates / Q000378:metabolism; D005269:Femur / Q000002:abnormalities / Q000737:chemistry / Q000378:metabolism*; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020894:Microfibrils / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics; D010710:Phosphates / Q000378:metabolism; D013314:Stress, Mechanical; D054159:Torsion, Mechanical; D054392:Adipokines
chemical_list: D002254:Carbonates; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D010710:Phosphates; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000605724:Fbn1 protein, mouse; C000605728:Fbn2 protein, mouse