title: Long bone maturation is driven by pore closing: A quantitative tomography investigation of structural formation in young C57BL/6 mice.
abstract: During mammalian growth, long bones undergo extensive structural reorganization, transforming from primitive shapes in the limb buds into mature bones. Here we shed light on the steps involved in structural formation of the mineralized tissue in midshafts of C57BL/6 femurs, shortly after birth. By combining 3D micrometer-resolution X-ray microtomography with 2D histology, we study the transformation of the tissue from a partially-mineralized scaffold into a compact bone structure. We identify three growth phases that take place during murine long bone maturation: During a patterning phase (I) mineralized struts form a loosely connected foam-like cortical network. During a transitioning phase (II), the extensive non-mineralized tracts vanish, transforming the foam into a fully continuous mass, by 14 days of age. Concomitantly, closed porosity increases to about ∼ 1.4%, and stays at this level, also found in maturity. During a shaping phase (III), the bones gradually attain their characteristic intricate adult form. Architectured mineral depositioning--first in open foamy scaffolds, and later into solid bone material--is presumably a compromise between the mechanical needs of providing support to the body, and the biological requirements of vascularization and extensive nutritional needs in the early stages of bone formation.
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, Research Campus Golm, 14476 Potsdam, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Emely.Bortel@mpikg.mpg.de.
authors.forename: Emely L
authors.initials: EL
authors.lastname: Bortel
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Georg.Duda@charite.de.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Ihnestraße 63-73, 14195 Berlin, Germany; Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Stefan.Mundlos@charite.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Bettina.Willie@charite.de.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Willie
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, Research Campus Golm, 14476 Potsdam, Germany. Electronic address: Fratzl@mpikg.mpg.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Fratzl
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: Paul.Zaslansky@charite.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Zaslansky
mesh_terms: D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000000981:diagnostic imaging*; D002113:Calcification, Physiologic; D005269:Femur / Q000000981:diagnostic imaging / Q000502:physiology; D021621:Imaging, Three-Dimensional; D008810:Mice, Inbred C57BL; D016062:Porosity; D015203:Reproducibility of Results; D055114:X-Ray Microtomography / Q000379:methods*
keywords: Bone; Histomorphometry; Microstructure; Organogenesis; Osteogenic patterning