Osteocyte-directed bone demineralization along canaliculi

• Published in: Bone (New York, N.Y.) N.Y.), 2016-03, Vol.84, p.279-288
• Main Authors: Nango, Nobuhito, Kubota, Shogo, Hasegawa, Tomoka, Yashiro, Wataru, Momose, Atsushi, Matsuo, Koichi
• Format: Article
• Language: English
• Subjects: Animals; Bone Demineralization, Pathologic - pathology; Bone Demineralization, Pathologic - physiopathology; Bone Density - drug effects; Demineralization/remineralization; Diaphyses - drug effects; Diaphyses - pathology; Female; Humans; Lactation - drug effects; Mice, Inbred C57BL; Mineral metabolism; Orthopedics; Osteocyte canaliculus; Osteocytes - drug effects; Osteocytes - metabolism; Osteocytes - pathology; Osteocytic osteolysis; Osteopetrosis - pathology; Osteopetrosis - physiopathology; Parathyroid Hormone - pharmacology; Periosteum - pathology; Periosteum - physiopathology; Proto-Oncogene Proteins c-fos - deficiency; Proto-Oncogene Proteins c-fos - metabolism; Synchrotron radiation; Synchrotrons; Talbot-defocus multiscan tomography; Tomography; X-Rays
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2015.12.006

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.