| Literature DB >> 33636130 |
Michelle M McDonald1, Weng Hua Khoo1, Pei Ying Ng2, Ya Xiao3, Jad Zamerli3, Peter Thatcher3, Wunna Kyaw4, Karrnan Pathmanandavel4, Abigail K Grootveld4, Imogen Moran4, Danyal Butt4, Akira Nguyen4, Alexander Corr1, Sean Warren5, Maté Biro6, Natalie C Butterfield7, Siobhan E Guilfoyle7, Davide Komla-Ebri7, Michael R G Dack7, Hannah F Dewhurst7, John G Logan7, Yongxiao Li8, Sindhu T Mohanty1, Niall Byrne1, Rachael L Terry1, Marija K Simic1, Ryan Chai3, Julian M W Quinn1, Scott E Youlten3, Jessica A Pettitt3, David Abi-Hanna1, Rohit Jain9, Wolfgang Weninger10, Mischa Lundberg11, Shuting Sun12, Frank H Ebetino12, Paul Timpson5, Woei Ming Lee8, Paul A Baldock1, Michael J Rogers1, Robert Brink13, Graham R Williams7, J H Duncan Bassett7, John P Kemp14, Nathan J Pavlos2, Peter I Croucher15, Tri Giang Phan16.
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.Entities:
Keywords: RANKL; cell fission; cellular recycling; denosumab; macrophage; osteoclast; osteomorph; osteoporosis; osteoprotegerin; skeletal dysplasia
Year: 2021 PMID： 33636130 PMCID： PMC7938889 DOI： 10.1016/j.cell.2021.02.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582