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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2021
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.
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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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