title: Osteocyte-directed bone demineralization along canaliculi.
abstract: The mammalian skeleton stores calcium and phosphate ions in bone matrix. Osteocytes in osteocyte lacunae extend numerous dendrites into canaliculi less than a micron in diameter and which are distributed throughout bone matrix. Although osteoclasts are the primary bone-resorbing cells, osteocytes also reportedly dissolve hydroxyapatite at peri-lacunar bone matrix. However, robust three-dimensional evidence for peri-canalicular bone mineral dissolution has been lacking. Here we applied a previously reported Talbot-defocus multiscan tomography method for synchrotron X-ray microscopy and analyzed the degree of bone mineralization in mouse cortical bone around the lacuno-canalicular network, which is connected both to blood vessels and the peri- and endosteum. We detected cylindrical low mineral density regions spreading around canaliculi derived from a subset of osteocytes. Transmission electron microscopy revealed both intact and demineralized bone matrix around the canaliculus. Peri-canalicular low mineral density regions were also observed in osteopetrotic mice lacking osteoclasts, indicating that osteoclasts are dispensable for peri-canalicular demineralization. These data suggest demineralization can occur from within bone through the canalicular system, and that peri-canalicular demineralization occurs not uniformly but directed by individual osteocytes. Blockade of peri-canalicular demineralization may be a therapeutic strategy to increase bone mass and quality.
authors.affiliation: Ratoc System Engineering Co., Ltd, Tokyo 112-0014, Japan. Electronic address: nango@ratoc.co.jp.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Nango
authors.affiliation: Ratoc System Engineering Co., Ltd, Tokyo 112-0014, Japan. Electronic address: s-kubota@ratoc.co.jp.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Department of Developmental Biology of Hard Tissue, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan. Electronic address: hasegawa@den.hokudai.ac.jp.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Miyagi 980-8577, Japan. Electronic address: wyashiro@tagen.tohoku.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yashiro
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Miyagi 980-8577, Japan. Electronic address: momose@tagen.tohoku.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
authors.affiliation: Laboratory of Cell and Tissue Biology, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: kmatsuo@keio.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000818:Animals; D018488:Bone Demineralization, Pathologic / Q000473:pathology* / Q000503:physiopathology; D015519:Bone Density / Q000187:drug effects; D018483:Diaphyses / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007774:Lactation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010022:Osteopetrosis / Q000473:pathology / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010521:Periosteum / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000378:metabolism; D017356:Synchrotrons; D014054:Tomography; D014965:X-Rays
chemical_list: D010281:Parathyroid Hormone; D016760:Proto-Oncogene Proteins c-fos
keywords: Demineralization/remineralization; Mineral metabolism; Osteocyte canaliculus; Osteocytic osteolysis; Synchrotron radiation; Talbot-defocus multiscan tomography