Osteoclasts Recycle Via Osteomorphs During RANKL-stimulated Bone Resorption

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2021 Feb 26

PMID 33636130

Citations 131

Authors

Michelle M McDonald

Weng Hua Khoo

Pei Ying Ng

Ya Xiao

Jad Zamerli

Peter Thatcher

Wunna Kyaw

Karrnan Pathmanandavel

Abigail K Grootveld

Imogen Moran

Danyal Butt

Akira Nguyen

Alexander Corr

Sean Warren

Mate Biro

Natalie C Butterfield

Siobhan E Guilfoyle

Davide Komla-Ebri

Michael R G Dack

Hannah F Dewhurst

John G Logan

Yongxiao Li

Sindhu T Mohanty

Niall Byrne

Rachael L Terry

Marija K Simic

Ryan Chai

Julian M W Quinn

Scott E Youlten

Jessica A Pettitt

David Abi-Hanna

Rohit Jain

Wolfgang Weninger

Mischa Lundberg

Shuting Sun

Frank H Ebetino

Paul Timpson

Woei Ming Lee

Paul A Baldock

Michael J Rogers

Robert Brink

Graham R Williams

J H Duncan Bassett

John P Kemp

Nathan J Pavlos

Peter I Croucher

Tri Giang Phan

Affiliations

Soon will be listed here.

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.

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