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Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.
McDonald, Michelle M; Khoo, Weng Hua; Ng, Pei Ying; Xiao, Ya; Zamerli, Jad; Thatcher, Peter; Kyaw, Wunna; Pathmanandavel, Karrnan; Grootveld, Abigail K; Moran, Imogen; Butt, Danyal; Nguyen, Akira; Corr, Alexander; Warren, Sean; Biro, Maté; Butterfield, Natalie C; Guilfoyle, Siobhan E; Komla-Ebri, Davide; Dack, Michael R G; Dewhurst, Hannah F; Logan, John G; Li, Yongxiao; Mohanty, Sindhu T; Byrne, Niall; Terry, Rachael L; Simic, Marija K; Chai, Ryan; Quinn, Julian M W; Youlten, Scott E; Pettitt, Jessica A; Abi-Hanna, David; Jain, Rohit; Weninger, Wolfgang; Lundberg, Mischa; Sun, Shuting; Ebetino, Frank H; Timpson, Paul; Lee, Woei Ming; Baldock, Paul A; Rogers, Michael J; Brink, Robert; Williams, Graham R; Bassett, J H Duncan; Kemp, John P; Pavlos, Nathan J; Croucher, Peter I; Phan, Tri Giang.
Afiliação
  • McDonald MM; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Khoo WH; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Ng PY; Bone Biology & Disease Laboratory, School of Biomedical Sciences, University of Western Australia, Nedlands, WA, Australia.
  • Xiao Y; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Zamerli J; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Thatcher P; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Kyaw W; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Pathmanandavel K; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Grootveld AK; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Moran I; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Butt D; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Nguyen A; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Corr A; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Warren S; Cancer, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Biro M; EMBL Australia, Single Molecule Science Node, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
  • Butterfield NC; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Guilfoyle SE; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Komla-Ebri D; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Dack MRG; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Dewhurst HF; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Logan JG; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Li Y; John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
  • Mohanty ST; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Byrne N; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Terry RL; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Simic MK; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Chai R; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Quinn JMW; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Youlten SE; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Pettitt JA; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Abi-Hanna D; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Jain R; Immune Imaging Program, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
  • Weninger W; Immune Imaging Program, Centenary Institute, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Lundberg M; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba, QLD, Australia; Transformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW, Australia.
  • Sun S; Biovinc, Pasadena, CA, USA.
  • Ebetino FH; Biovinc, Pasadena, CA, USA.
  • Timpson P; Cancer, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Lee WM; John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
  • Baldock PA; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Rogers MJ; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
  • Brink R; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Williams GR; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Bassett JHD; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
  • Kemp JP; The University of Queensland Diamantina Institute, University of Queensland, Woolloongabba, QLD, Australia; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Pavlos NJ; Bone Biology & Disease Laboratory, School of Biomedical Sciences, University of Western Australia, Nedlands, WA, Australia.
  • Croucher PI; Healthy Ageing Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia. Electronic address: p.croucher@garvan.org.au.
  • Phan TG; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia; Immunology Theme, Garvan Institute of Medical Research, Sydney, NSW, Australia. Electronic address: t.phan@garvan.org.au.
Cell ; 184(5): 1330-1347.e13, 2021 03 04.
Article em En | MEDLINE | ID: mdl-33636130
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoclastos / Reabsorção Óssea / Ligante RANK Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteoclastos / Reabsorção Óssea / Ligante RANK Idioma: En Ano de publicação: 2021 Tipo de documento: Article