ELMO1 signaling is a promoter of osteoclast function and bone loss.

Szczegóły
Abstrakt

Tytuł:: ELMO1 signaling is a promoter of osteoclast function and bone loss.
Autorzy:: Arandjelovic S; Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology and Carter Immunology Center, University of Virginia, Charlottesville, VA, USA. .
Perry JSA; Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology and Carter Immunology Center, University of Virginia, Charlottesville, VA, USA.
Zhou M; Inova Schar Cancer Institute, Inova Center for Personalized Health, Fairfax, VA, USA.
Ceroi A; Inflammation Research Centre, VIB, and the Department of Biomedical Molecular Biology, Ghent Univeristy, Ghent, Belgium.
Smirnov I; Brain Inflammation and Glia Center and Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
Walk SF; Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology and Carter Immunology Center, University of Virginia, Charlottesville, VA, USA.
Shankman LS; Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology and Carter Immunology Center, University of Virginia, Charlottesville, VA, USA.
Cambré I; Inflammation Research Centre, VIB, and the Department of Biomedical Molecular Biology, Ghent Univeristy, Ghent, Belgium.
Onengut-Gumuscu S; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Elewaut D; Inflammation Research Centre, VIB, and the Department of Biomedical Molecular Biology, Ghent Univeristy, Ghent, Belgium.
Conrads TP; Inova Schar Cancer Institute, Inova Center for Personalized Health, Fairfax, VA, USA.
Ravichandran KS; Center for Cell Clearance, Department of Microbiology, Immunology, and Cancer Biology and Carter Immunology Center, University of Virginia, Charlottesville, VA, USA. .; Inflammation Research Centre, VIB, and the Department of Biomedical Molecular Biology, Ghent Univeristy, Ghent, Belgium. .
Źródło:: Nature communications [Nat Commun] 2021 Aug 17; Vol. 12 (1), pp. 4974. Date of Electronic Publication: 2021 Aug 17.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Signal Transduction*
Adaptor Proteins, Signal Transducing/*genetics
Adaptor Proteins, Signal Transducing/*metabolism
Bone Diseases, Metabolic/*metabolism
Osteoclasts/*metabolism
Osteoporosis/*metabolism
Adaptor Proteins, Signal Transducing/deficiency ; Animals ; Arthritis/pathology ; Bone Resorption/metabolism ; CRISPR-Cas Systems ; Female ; Mice ; Mice, Knockout ; Osteoprotegerin/deficiency ; Ovariectomy ; Transcriptome ; X-Ray Microtomography
References:: Curr Biol. 2005 Feb 22;15(4):371-7. (PMID: 15723800)
Bonekey Rep. 2014 Sep 10;3:570. (PMID: 25228983)
Cell. 1996 Nov 29;87(5):811-22. (PMID: 8945509)
Immunity. 1999 Apr;10(4):451-61. (PMID: 10229188)
Int J Mol Sci. 2018 Mar 26;19(4):. (PMID: 29587415)
Immunity. 2014 Sep 18;41(3):414-426. (PMID: 25220213)
J Histochem Cytochem. 1959 Jan;7(1):39-41. (PMID: 13664936)
Methods. 2015 Mar;74:83-9. (PMID: 25484339)
J Bone Miner Res. 2018 Oct;33(10):1773-1784. (PMID: 29750835)
Invert Neurosci. 2018 Nov 28;19(1):1. (PMID: 30488358)
Genes Dev. 1998 May 1;12(9):1260-8. (PMID: 9573043)
Cell. 2001 Oct 5;107(1):27-41. (PMID: 11595183)
Curr Stem Cell Res Ther. 2016;11(8):626-633. (PMID: 26477623)
Bonekey Rep. 2014 Dec 10;3:614. (PMID: 25852854)
Nucleic Acids Res. 2015 Jan;43(Database issue):D726-36. (PMID: 25348401)
Nucleic Acids Res. 2012 Jan;40(Database issue):D1047-54. (PMID: 22139925)
Sci Rep. 2015 Nov 04;5:16124. (PMID: 26530337)
Trends Cell Biol. 2011 Jan;21(1):20-8. (PMID: 20961760)
Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3305-10. (PMID: 22331897)
Nucleic Acids Res. 2009 Jan;37(Database issue):D786-92. (PMID: 18782832)
Int J Biochem Cell Biol. 2012 Sep;44(9):1422-35. (PMID: 22652318)
Bone. 2010 Apr;46(4):911-9. (PMID: 19716455)
Nucleic Acids Res. 2003 Jan 1;31(1):193-5. (PMID: 12519980)
Nat Struct Mol Biol. 2004 Aug;11(8):756-62. (PMID: 15247908)
Clin Chem. 1998 Nov;44(11):2281-9. (PMID: 9799755)
Rheumatology (Oxford). 2016 Dec;55(suppl 2):ii61-ii63. (PMID: 27856662)
FEBS Lett. 2008 Apr 30;582(10):1451-8. (PMID: 18381073)
Clin Chem. 1998 Nov;44(11):2290-300. (PMID: 9799756)
N Engl J Med. 2004 Dec 30;351(27):2839-49. (PMID: 15625335)
Front Physiol. 2017 Jun 06;8:371. (PMID: 28634454)
Nat Med. 2015 Mar;21(3):212-3. (PMID: 25742453)
Autoimmunity. 2008 Apr;41(3):183-94. (PMID: 18365831)
Eur J Rheumatol. 2017 Mar;4(1):46-56. (PMID: 28293453)
PLoS Genet. 2019 May 1;15(5):e1008123. (PMID: 31042701)
FASEB J. 2009 Dec;23(12):4081-90. (PMID: 19667119)
Nat Protoc. 2007;2(5):1269-75. (PMID: 17546023)
J Biol Chem. 2004 Feb 13;279(7):6087-97. (PMID: 14638695)
Nat Cell Biol. 2002 Aug;4(8):574-82. (PMID: 12134158)
Rheumatology (Oxford). 2012 Dec;51(12):2252-61. (PMID: 22942404)
Nat Immunol. 2019 Feb;20(2):141-151. (PMID: 30643265)
J Biochem. 1998 Apr;123(4):752-9. (PMID: 9538271)
Nucleic Acids Res. 2017 Jan 4;45(D1):D362-D368. (PMID: 27924014)
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4489-94. (PMID: 11904364)
J Cell Biol. 2003 Aug 4;162(3):499-509. (PMID: 12900398)
Calcif Tissue Int. 2008 Feb;82(2):108-15. (PMID: 18084692)
Nat Commun. 2015 Mar 31;6:6651. (PMID: 25825024)
Nucleic Acids Res. 2015 Jan;43(Database issue):D914-20. (PMID: 25326323)
J Rheumatol Suppl. 2004 Mar;69:55-65. (PMID: 15053455)
Nature. 2010 Sep 16;467(7313):333-7. (PMID: 20844538)
Nat Methods. 2006 Apr;3(4):287-93. (PMID: 16554834)
Arthritis Res Ther. 2007;9(1):203. (PMID: 17316459)
Grant Information:: K99 CA237728 United States CA NCI NIH HHS; R35 GM122542 United States GM NIGMS NIH HHS; T32 CA009109 United States CA NCI NIH HHS
Substance Nomenclature:: 0 (Adaptor Proteins, Signal Transducing)
0 (ELMO1 protein, mouse)
0 (Osteoprotegerin)
Entry Date(s):: Date Created: 20210818 Date Completed: 20210830 Latest Revision: 20210904
Update Code:: 20240104
PubMed Central ID:: PMC8371122
DOI:: 10.1038/s41467-021-25239-6
PMID:: 34404802
: Czasopismo naukowe

Full Text Finder

Osteoporosis affects millions worldwide and is often caused by osteoclast induced bone loss. Here, we identify the cytoplasmic protein ELMO1 as an important 'signaling node' in osteoclasts. We note that ELMO1 SNPs associate with bone abnormalities in humans, and that ELMO1 deletion in mice reduces bone loss in four in vivo models: osteoprotegerin deficiency, ovariectomy, and two types of inflammatory arthritis. Our transcriptomic analyses coupled with CRISPR/Cas9 genetic deletion identify Elmo1 associated regulators of osteoclast function, including cathepsin G and myeloperoxidase. Further, we define the 'ELMO1 interactome' in osteoclasts via proteomics and reveal proteins required for bone degradation. ELMO1 also contributes to osteoclast sealing zone on bone-like surfaces and distribution of osteoclast-specific proteases. Finally, a 3D structure-based ELMO1 inhibitory peptide reduces bone resorption in wild type osteoclasts. Collectively, we identify ELMO1 as a signaling hub that regulates osteoclast function and bone loss, with relevance to osteoporosis and arthritis.
(© 2021. The Author(s).)

Informacja