Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.cell.2021.02.002
Journal or Publication Title: Cell
Volume: 184
Number: 5
Page Range: 1330-1347.e13
Date: 2021
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1016/j.cell.2021.02.002
ISSN: 00928674
Date Deposited: 10 Jun 2021 00:01
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.

Keywords: RANKL; cell fission; cellular recycling; denosumab; macrophage; osteoclast; osteomorph; osteoporosis; osteoprotegerin; skeletal dysplasia.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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McDonald, Michelle M.
UNSPECIFIED
Khoo, Weng Hua
UNSPECIFIED
Ng, Pei Ying
UNSPECIFIED
Xiao, Ya
UNSPECIFIED
Zamerli, Jad
UNSPECIFIED
Thatcher, Peter
UNSPECIFIED
Kyaw, Wunna
UNSPECIFIED
Pathmanandavel, Karrnan
UNSPECIFIED
Grootveld, Abigail K.
UNSPECIFIED
Moran, Imogen
UNSPECIFIED
Butt, Danyal
UNSPECIFIED
Nguyen, Akira
UNSPECIFIED
Corr, Alexander
UNSPECIFIED
Warren, Sean
UNSPECIFIED
Biro, Maté
UNSPECIFIED
Butterfield, Natalie C.
UNSPECIFIED
Guilfoyle, Siobhan E.
UNSPECIFIED
Komla-Ebri, Davide
UNSPECIFIED
Dack, Michael R.G.
UNSPECIFIED
Dewhurst, Hannah F.
UNSPECIFIED
Logan, John G.
UNSPECIFIED
Li, Yongxiao
UNSPECIFIED
Mohanty, Sindhu T.
UNSPECIFIED
Byrne, Niall
UNSPECIFIED
Terry, Rachael L.
UNSPECIFIED
Simic, Marija K.
UNSPECIFIED
Chai, Ryan
UNSPECIFIED
Quinn, Julian M.W.
UNSPECIFIED
Youlten, Scott E.
UNSPECIFIED
Pettitt, Jessica A.
UNSPECIFIED
Abi-Hanna, David
UNSPECIFIED
Jain, Rohit
UNSPECIFIED
Weninger, Wolfgang
UNSPECIFIED
Lundberg, Mischa
UNSPECIFIED
Sun, Shuting
UNSPECIFIED
Ebetino, Frank H.
UNSPECIFIED
Timpson, Paul
UNSPECIFIED
Lee, Woei Ming
UNSPECIFIED
Baldock, Paul A.
UNSPECIFIED
Rogers, Michael J.
UNSPECIFIED
Brink, Robert
UNSPECIFIED
Williams, Graham R.
UNSPECIFIED
Bassett, J.H. Duncan
UNSPECIFIED
Kemp, John P.
UNSPECIFIED
Pavlos, Nathan J.
UNSPECIFIED
Croucher, Peter I.
UNSPECIFIED
Phan, Tri Giang
UNSPECIFIED
Last Modified: 10 Jun 2021 00:01
URI: https://eprints.centenary.org.au/id/eprint/1012

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