TY - JOUR
T1 - The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption
AU - Delaisse, Jean Marie
AU - Søe, Kent
AU - Andersen, Thomas Levin
AU - Rojek, Aleksandra Maria
AU - Marcussen, Niels
N1 - Publisher Copyright:
© Copyright © 2021 Delaisse, Søe, Andersen, Rojek and Marcussen.
PY - 2021/3
Y1 - 2021/3
N2 - The current models of osteoclastic bone resorption focus on immobile osteoclasts sitting on the bone surface and drilling a pit into the bone matrix. It recently appeared that many osteoclasts also enlarge their pit by moving across the bone surface while resorbing. Drilling a pit thus represents only the start of a resorption event of much larger amplitude. This prolonged resorption activity significantly contributes to pathological bone destruction, but the mechanism whereby the osteoclast engages in this process does not have an answer within the standard bone resorption models. Herein, we review observations that lead to envision how prolonged resorption is possible through simultaneous resorption and migration. According to the standard pit model, the “sealing zone” which surrounds the ruffled border (i.e., the actual resorption apparatus), “anchors” the ruffled border against the bone surface to be resorbed. Herein, we highlight that continuation of resorption demands that the sealing zone “glides” inside the cavity. Thereby, the sealing zone emerges as the structure responsible for orienting and displacing the ruffled border, e.g., directing resorption against the cavity wall. Importantly, sealing zone displacement stringently requires thorough collagen removal from the cavity wall - which renders strong cathepsin K collagenolysis indispensable for engagement of osteoclasts in cavity-enlargement. Furthermore, the sealing zone is associated with generation of new ruffled border at the leading edge, thereby allowing the ruffled border to move ahead. The sealing zone and ruffled border displacements are coordinated with the migration of the cell body, shown to be under control of lamellipodia at the leading edge and of the release of resorption products at the rear. We propose that bone resorption demands more attention to osteoclastic models integrating resorption and migration activities into just one cell phenotype.
AB - The current models of osteoclastic bone resorption focus on immobile osteoclasts sitting on the bone surface and drilling a pit into the bone matrix. It recently appeared that many osteoclasts also enlarge their pit by moving across the bone surface while resorbing. Drilling a pit thus represents only the start of a resorption event of much larger amplitude. This prolonged resorption activity significantly contributes to pathological bone destruction, but the mechanism whereby the osteoclast engages in this process does not have an answer within the standard bone resorption models. Herein, we review observations that lead to envision how prolonged resorption is possible through simultaneous resorption and migration. According to the standard pit model, the “sealing zone” which surrounds the ruffled border (i.e., the actual resorption apparatus), “anchors” the ruffled border against the bone surface to be resorbed. Herein, we highlight that continuation of resorption demands that the sealing zone “glides” inside the cavity. Thereby, the sealing zone emerges as the structure responsible for orienting and displacing the ruffled border, e.g., directing resorption against the cavity wall. Importantly, sealing zone displacement stringently requires thorough collagen removal from the cavity wall - which renders strong cathepsin K collagenolysis indispensable for engagement of osteoclasts in cavity-enlargement. Furthermore, the sealing zone is associated with generation of new ruffled border at the leading edge, thereby allowing the ruffled border to move ahead. The sealing zone and ruffled border displacements are coordinated with the migration of the cell body, shown to be under control of lamellipodia at the leading edge and of the release of resorption products at the rear. We propose that bone resorption demands more attention to osteoclastic models integrating resorption and migration activities into just one cell phenotype.
KW - cathepsin K
KW - collagen
KW - osteoclast
KW - osteoporosis
KW - resorption trenches
KW - ruffled border
KW - sealing zone
UR - https://www.scopus.com/pages/publications/85104059940
U2 - 10.3389/fcell.2021.644503
DO - 10.3389/fcell.2021.644503
M3 - Journal article
C2 - 33859985
AN - SCOPUS:85104059940
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 644503
ER -