Osteocyte-directed bone demineralization along canaliculi

Bone. 2016 Mar;84:279-288. doi: 10.1016/j.bone.2015.12.006. Epub 2015 Dec 17.

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.

Keywords: Demineralization/remineralization; Mineral metabolism; Osteocyte canaliculus; Osteocytic osteolysis; Synchrotron radiation; Talbot-defocus multiscan tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Demineralization, Pathologic / pathology*
  • Bone Demineralization, Pathologic / physiopathology
  • Bone Density / drug effects
  • Diaphyses / drug effects
  • Diaphyses / pathology
  • Female
  • Humans
  • Lactation / drug effects
  • Mice, Inbred C57BL
  • Osteocytes / drug effects
  • Osteocytes / metabolism
  • Osteocytes / pathology*
  • Osteopetrosis / pathology
  • Osteopetrosis / physiopathology
  • Parathyroid Hormone / pharmacology
  • Periosteum / pathology
  • Periosteum / physiopathology
  • Proto-Oncogene Proteins c-fos / deficiency
  • Proto-Oncogene Proteins c-fos / metabolism
  • Synchrotrons
  • Tomography
  • X-Rays

Substances

  • Parathyroid Hormone
  • Proto-Oncogene Proteins c-fos