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.

Lactation-Induced Changes in the Volume of Osteocyte Lacunar-Canalicular Space Alter Mechanical Properties in Cortical Bone Tissue

“…Calcium and phosphates along the LCS walls appear to be more labile and readily exchanged with the bone fluid. (59) Nango and colleagues (31) recently confirmed the existence of a small zone of mineral on canalicular walls that is rapidly mobilized in lactation and other stress states. Together, these data indicate that there are no changes in the overall mineral content of bone matrix after lactation in mouse, and so bulk changes in mineralization do not contribute to the changes in bone tissue material properties seen with lactation and recovery.…”

“…The need to release mineral, rather than matrix constituents, from bone has long been considered the primary driver of osteocytic osteolysis, (6,8,10,31,53,63–67) and presumably such rapid mineral removal occurs through acidification of the fluid in the LCS. Data to support LCS acidification during lactation are lacking, but the ability of osteocytes to acidify their local microenvironment was recently demonstrated in sciatic neurectomy.…”

Bone Alkaline Phosphatase and Tartrate-Resistant Acid Phosphatase: Potential Co-regulators of Bone Mineralization

“…There are data suggesting that osteocytes remodel its lacunae and canaliculae [36, 37], which involves similar mechanisms that osteoclasts use for resorbing bone (i.e., acidification, demineralization, and collagen degradation). The subsequent formation process in the osteocyte lacuna remains elusive; however, we suggest that this process could be mediated by TRAP, instead of BALP, in controlling the inhibitory effect of PPi and/or OPN.…”

Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

“…50,51 Qing et al 52 reported that tartrate-resistant acid phosphatase and cathepsin K were involved in osteocytic osteolysis. They also reported that no osteocytic remodeling was observed with experimental unloading.…”