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Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption
Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938889/ https://www.ncbi.nlm.nih.gov/pubmed/33636130 http://dx.doi.org/10.1016/j.cell.2021.02.002 |
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author | McDonald, Michelle M. Khoo, Weng Hua Ng, Pei Ying Xiao, Ya Zamerli, Jad Thatcher, Peter Kyaw, Wunna Pathmanandavel, Karrnan Grootveld, Abigail K. Moran, Imogen Butt, Danyal Nguyen, Akira Warren, Sean Biro, Maté Butterfield, Natalie C. Guilfoyle, Siobhan E. Komla-Ebri, Davide Dack, Michael R.G. Dewhurst, Hannah F. Logan, John G. Li, Yongxiao Mohanty, Sindhu T. Byrne, Niall Terry, Rachael L. Simic, Marija K. Chai, Ryan Quinn, Julian M.W. Youlten, Scott E. Pettitt, Jessica A. Abi-Hanna, David Jain, Rohit Weninger, Wolfgang Lundberg, Mischa Sun, Shuting Ebetino, Frank H. Timpson, Paul Lee, Woei Ming Baldock, Paul A. Rogers, Michael J. Brink, Robert Williams, Graham R. Bassett, J.H. Duncan Kemp, John P. Pavlos, Nathan J. Croucher, Peter I. Phan, Tri Giang |
author_facet | McDonald, Michelle M. Khoo, Weng Hua Ng, Pei Ying Xiao, Ya Zamerli, Jad Thatcher, Peter Kyaw, Wunna Pathmanandavel, Karrnan Grootveld, Abigail K. Moran, Imogen Butt, Danyal Nguyen, Akira Warren, Sean Biro, Maté Butterfield, Natalie C. Guilfoyle, Siobhan E. Komla-Ebri, Davide Dack, Michael R.G. Dewhurst, Hannah F. Logan, John G. Li, Yongxiao Mohanty, Sindhu T. Byrne, Niall Terry, Rachael L. Simic, Marija K. Chai, Ryan Quinn, Julian M.W. Youlten, Scott E. Pettitt, Jessica A. Abi-Hanna, David Jain, Rohit Weninger, Wolfgang Lundberg, Mischa Sun, Shuting Ebetino, Frank H. Timpson, Paul Lee, Woei Ming Baldock, Paul A. Rogers, Michael J. Brink, Robert Williams, Graham R. Bassett, J.H. Duncan Kemp, John P. Pavlos, Nathan J. Croucher, Peter I. Phan, Tri Giang |
author_sort | McDonald, Michelle M. |
collection | PubMed |
description | Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases. |
format | Online Article Text |
id | pubmed-7938889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-79388892021-03-16 Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption McDonald, Michelle M. Khoo, Weng Hua Ng, Pei Ying Xiao, Ya Zamerli, Jad Thatcher, Peter Kyaw, Wunna Pathmanandavel, Karrnan Grootveld, Abigail K. Moran, Imogen Butt, Danyal Nguyen, Akira Warren, Sean Biro, Maté Butterfield, Natalie C. Guilfoyle, Siobhan E. Komla-Ebri, Davide Dack, Michael R.G. Dewhurst, Hannah F. Logan, John G. Li, Yongxiao Mohanty, Sindhu T. Byrne, Niall Terry, Rachael L. Simic, Marija K. Chai, Ryan Quinn, Julian M.W. Youlten, Scott E. Pettitt, Jessica A. Abi-Hanna, David Jain, Rohit Weninger, Wolfgang Lundberg, Mischa Sun, Shuting Ebetino, Frank H. Timpson, Paul Lee, Woei Ming Baldock, Paul A. Rogers, Michael J. Brink, Robert Williams, Graham R. Bassett, J.H. Duncan Kemp, John P. Pavlos, Nathan J. Croucher, Peter I. Phan, Tri Giang Cell Article Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases. Cell Press 2021-03-04 /pmc/articles/PMC7938889/ /pubmed/33636130 http://dx.doi.org/10.1016/j.cell.2021.02.002 Text en © 2021 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article McDonald, Michelle M. Khoo, Weng Hua Ng, Pei Ying Xiao, Ya Zamerli, Jad Thatcher, Peter Kyaw, Wunna Pathmanandavel, Karrnan Grootveld, Abigail K. Moran, Imogen Butt, Danyal Nguyen, Akira Warren, Sean Biro, Maté Butterfield, Natalie C. Guilfoyle, Siobhan E. Komla-Ebri, Davide Dack, Michael R.G. Dewhurst, Hannah F. Logan, John G. Li, Yongxiao Mohanty, Sindhu T. Byrne, Niall Terry, Rachael L. Simic, Marija K. Chai, Ryan Quinn, Julian M.W. Youlten, Scott E. Pettitt, Jessica A. Abi-Hanna, David Jain, Rohit Weninger, Wolfgang Lundberg, Mischa Sun, Shuting Ebetino, Frank H. Timpson, Paul Lee, Woei Ming Baldock, Paul A. Rogers, Michael J. Brink, Robert Williams, Graham R. Bassett, J.H. Duncan Kemp, John P. Pavlos, Nathan J. Croucher, Peter I. Phan, Tri Giang Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title | Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title_full | Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title_fullStr | Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title_full_unstemmed | Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title_short | Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption |
title_sort | osteoclasts recycle via osteomorphs during rankl-stimulated bone resorption |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938889/ https://www.ncbi.nlm.nih.gov/pubmed/33636130 http://dx.doi.org/10.1016/j.cell.2021.02.002 |
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