作者
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, Maté Biro, Natalie C Butterfield, Siobhan E Guilfoyle, Davide Komla-Ebri, Michael RG Dack, Hannah F Dewhurst, John G Logan, Yongxiao Li, Sindhu T Mohanty, Niall Byrne, Rachael L Terry, Marija K Simic, Ryan Chai, Julian MW 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, JH Duncan Bassett, John P Kemp, Nathan J Pavlos, Peter I Croucher, Tri Giang Phan
发表日期
2021/3/4
期刊
Cell
卷号
184
期号
5
页码范围
1330-1347. e13
出版商
Elsevier
简介
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 …
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