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Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

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Title: Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption
Authors: McDonald, MM
Khoo, WH
Ng, PY
Xiao, Y
Zamerli, J
Thatcher, P
Kyaw, W
Pathmanandavel, K
Grootveld, AK
Moran, I
Butt, D
Nguyen, A
Corr, A
Warren, S
Biro, M
Butterfield, NC
Guilfoyle, SE
Komla-Ebri, D
Dack, MRG
Dewhurst, HF
Logan, JG
Li, Y
Mohanty, ST
Byrne, N
Terry, RL
Simic, MK
Chai, R
Quinn, JMW
Youlten, SE
Pettitt, JA
Abi-Hanna, D
Jain, R
Weninger, W
Lundberg, M
Sun, S
Ebetino, FH
Timpson, P
Lee, WM
Baldock, PA
Rogers, MJ
Brink, R
Williams, GR
Bassett, JHD
Kemp, JP
Pavlos, NJ
Croucher, P
Phan, TG
Item Type: Journal Article
Abstract: 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.
Issue Date: 4-Mar-2021
Date of Acceptance: 1-Feb-2021
URI: http://hdl.handle.net/10044/1/87656
DOI: 10.1016/j.cell.2021.02.002
ISSN: 0092-8674
Publisher: Cell Press
Start Page: 1330
End Page: 1347.e13
Journal / Book Title: Cell
Volume: 184
Issue: 5
Copyright Statement: © 2021 The Authors. Published by Elsevier Inc.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 101123/Z/13/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
cell fission
cellular recycling
skeletal dysplasia
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2021-02-25
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine

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