The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption
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 on...
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| Format: | Article |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.644503/full |
| _version_ | 1818579339024793600 |
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| author | Jean-Marie Delaisse Jean-Marie Delaisse Jean-Marie Delaisse Kent Søe Kent Søe Kent Søe Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Aleksandra Maria Rojek Niels Marcussen |
| author_facet | Jean-Marie Delaisse Jean-Marie Delaisse Jean-Marie Delaisse Kent Søe Kent Søe Kent Søe Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Aleksandra Maria Rojek Niels Marcussen |
| author_sort | Jean-Marie Delaisse |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T07:00:07Z |
| format | Article |
| id | doaj.art-2b2e8228219f4f88b11df243dfc6830c |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T07:00:07Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2b2e8228219f4f88b11df243dfc6830c2022-12-21T22:40:11ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.644503644503The Mechanism Switching the Osteoclast From Short to Long Duration Bone ResorptionJean-Marie Delaisse0Jean-Marie Delaisse1Jean-Marie Delaisse2Kent Søe3Kent Søe4Kent Søe5Thomas Levin Andersen6Thomas Levin Andersen7Thomas Levin Andersen8Thomas Levin Andersen9Aleksandra Maria Rojek10Niels Marcussen11Clinical Cell Biology, Department of Pathology, Odense University Hospital, Odense, DenmarkClinical Cell Biology, Pathology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkClinical Cell Biology, Department of Pathology, Odense University Hospital, Odense, DenmarkClinical Cell Biology, Pathology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkClinical Cell Biology, Department of Pathology, Odense University Hospital, Odense, DenmarkClinical Cell Biology, Pathology Research Unit, Department of Clinical Research, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkDepartment of Forensic Medicine, Aarhus University, Aarhus, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkDepartment of Molecular Medicine, University of Southern Denmark, Odense, DenmarkThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.644503/fullosteoporosisruffled borderresorption trenchescathepsin Kcollagensealing zone |
| spellingShingle | Jean-Marie Delaisse Jean-Marie Delaisse Jean-Marie Delaisse Kent Søe Kent Søe Kent Søe Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Thomas Levin Andersen Aleksandra Maria Rojek Niels Marcussen The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption Frontiers in Cell and Developmental Biology osteoporosis ruffled border resorption trenches cathepsin K collagen sealing zone |
| title | The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption |
| title_full | The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption |
| title_fullStr | The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption |
| title_full_unstemmed | The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption |
| title_short | The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption |
| title_sort | mechanism switching the osteoclast from short to long duration bone resorption |
| topic | osteoporosis ruffled border resorption trenches cathepsin K collagen sealing zone |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.644503/full |
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