Osteoclasts adapt to physioxia perturbation through DNA demethylation.
bone metabolism
epigenetic regulation
intravital imaging
osteoclast
oxygen
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 12 2021
06 12 2021
Historique:
revised:
03
09
2021
received:
09
04
2021
accepted:
16
09
2021
pubmed:
19
10
2021
medline:
15
3
2022
entrez:
18
10
2021
Statut:
ppublish
Résumé
Oxygen plays an important role in diverse biological processes. However, since quantitation of the partial pressure of cellular oxygen in vivo is challenging, the extent of oxygen perturbation in situ and its cellular response remains underexplored. Using two-photon phosphorescence lifetime imaging microscopy, we determine the physiological range of oxygen tension in osteoclasts of live mice. We find that oxygen tension ranges from 17.4 to 36.4 mmHg, under hypoxic and normoxic conditions, respectively. Physiological normoxia thus corresponds to 5% and hypoxia to 2% oxygen in osteoclasts. Hypoxia in this range severely limits osteoclastogenesis, independent of energy metabolism and hypoxia-inducible factor activity. We observe that hypoxia decreases ten-eleven translocation (TET) activity. Tet2/3 cooperatively induces Prdm1 expression via oxygen-dependent DNA demethylation, which in turn activates NFATc1 required for osteoclastogenesis. Taken together, our results reveal that TET enzymes, acting as functional oxygen sensors, regulate osteoclastogenesis within the physiological range of oxygen tension, thus opening new avenues for research on in vivo response to oxygen perturbation.
Identifiants
pubmed: 34661337
doi: 10.15252/embr.202153035
pmc: PMC8647016
doi:
Substances chimiques
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e53035Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Références
Nat Med. 2007 Jul;13(7):791-801
pubmed: 17618270
Gene Ther. 2000 Jun;7(12):1063-6
pubmed: 10871756
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8673-8
pubmed: 24912186
Bioinformatics. 2014 Jan 15;30(2):284-6
pubmed: 24227674
Science. 2019 Mar 15;363(6432):1217-1222
pubmed: 30872525
Nat Med. 2009 Mar;15(3):259-66
pubmed: 19252502
J Bone Miner Res. 2018 Oct;33(10):1785-1798
pubmed: 29893999
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Trends Mol Med. 2002;8(4 Suppl):S62-7
pubmed: 11927290
Cancer Res. 2000 Aug 1;60(15):4010-5
pubmed: 10945599
Nature. 2003 May 15;423(6937):337-42
pubmed: 12748652
Nature. 1999 May 20;399(6733):271-5
pubmed: 10353251
Immunity. 2014 Oct 16;41(4):518-28
pubmed: 25367569
Biochim Biophys Acta. 2011 Mar;1807(3):348-58
pubmed: 21211514
J Bone Miner Metab. 2014 May;32(3):331-6
pubmed: 24366621
Science. 1988 Sep 23;241(4873):1649-51
pubmed: 3420417
Nat Commun. 2021 Apr 9;12(1):2136
pubmed: 33837198
J Bone Miner Metab. 2021 May;39(3):353-359
pubmed: 33106978
Endocrinology. 2014 May;155(5):1589-95
pubmed: 24437492
Nat Immunol. 2020 Aug;21(8):950-961
pubmed: 32572241
Nat Rev Immunol. 2007 Apr;7(4):292-304
pubmed: 17380158
Nature. 2016 Sep 1;537(7618):63-68
pubmed: 27533040
Proc Natl Acad Sci U S A. 1993 May 1;90(9):4304-8
pubmed: 8387214
Nat Med. 2012 Feb 19;18(3):405-12
pubmed: 22344299
J Biol Chem. 2016 Feb 19;291(8):4256-65
pubmed: 26703470
Immunity. 2013 Jan 24;38(1):79-91
pubmed: 23273845
J Biol Chem. 1987 Apr 25;262(12):5476-82
pubmed: 3571219
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4
pubmed: 7539918
Nat Med. 2015 Mar;21(3):281-7
pubmed: 25706873
J Cell Physiol. 2003 Jul;196(1):2-8
pubmed: 12767036
EMBO Rep. 2021 Dec 6;22(12):e53035
pubmed: 34661337
EMBO J. 1998 Jun 1;17(11):3005-15
pubmed: 9606183
ACS Chem Biol. 2011 Jul 15;6(7):709-15
pubmed: 21488691
J Clin Invest. 2013 Feb;123(2):866-73
pubmed: 23321670
Biochem Biophys Res Commun. 2005 Mar 25;328(4):885-94
pubmed: 15707961
Immunity. 2017 Jul 18;47(1):66-79.e5
pubmed: 28723554
J Biol Chem. 2003 Aug 15;278(33):30772-80
pubmed: 12788921
Sci Rep. 2018 May 14;8(1):7504
pubmed: 29760402
Nat Cell Biol. 2000 Jul;2(7):423-7
pubmed: 10878807
FEBS J. 2020 Sep;287(18):3888-3906
pubmed: 32446269
Cold Spring Harb Symp Quant Biol. 2013;78:1-10
pubmed: 24619230
Nature. 2014 Apr 10;508(7495):269-73
pubmed: 24590072
Nat Med. 2014 Nov;20(11):1270-8
pubmed: 25282358
Anal Chem. 2015 Mar 3;87(5):2710-7
pubmed: 25634116
Nature. 2010 Aug 26;466(7310):1129-33
pubmed: 20639862
Science. 2019 Mar 15;363(6432):1222-1226
pubmed: 30872526
J Clin Invest. 2007 Jun;117(6):1616-26
pubmed: 17549257
Nature. 2012 May 3;485(7396):69-74
pubmed: 22522930
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1171-7
pubmed: 20153717
Gynecol Oncol. 1998 Nov;71(2):270-7
pubmed: 9826471
Sci Rep. 2015 Dec 08;5:17838
pubmed: 26644023
Endocr Rev. 2017 Jun 1;38(3):255-266
pubmed: 28472361
Anal Chem. 2015 Jun 16;87(12):6371-9
pubmed: 25973679
Nat Commun. 2013;4:1950
pubmed: 23727690
Angew Chem Int Ed Engl. 2015 Jul 13;54(29):8340-62
pubmed: 26084034
Cancer Cell. 2010 Dec 14;18(6):553-67
pubmed: 21130701
Nat Rev Genet. 2003 Aug;4(8):638-49
pubmed: 12897775
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3117-22
pubmed: 20133620
Mol Cell. 2010 Oct 22;40(2):294-309
pubmed: 20965423
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Front Immunol. 2020 Jul 21;11:1405
pubmed: 32793196
Nat Commun. 2016 May 18;7:11635
pubmed: 27189088
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Science. 2001 Apr 20;292(5516):468-72
pubmed: 11292861
J Cell Sci. 2009 Jul 15;122(Pt 14):2504-13
pubmed: 19549681
Chem Sci. 2013 Aug 1;4(8):3110-3117
pubmed: 26682036
J Exp Med. 2010 Apr 12;207(4):751-62
pubmed: 20368579
Genomics Proteomics Bioinformatics. 2018 Jun;16(3):172-186
pubmed: 29908294
J Biophotonics. 2016 Aug;9(8):800-11
pubmed: 26990032
Blood. 2007 Apr 15;109(8):3253-9
pubmed: 17158225
Commun Biol. 2020 Sep 8;3(1):496
pubmed: 32901092
Mol Cell Biol. 2016 May 16;36(11):1610-20
pubmed: 27001307
J Clin Invest. 2018 Mar 1;128(3):1087-1105
pubmed: 29431735
Cell Rep. 2019 Sep 10;28(11):2923-2938.e8
pubmed: 31509752
Sci Rep. 2020 Dec 3;10(1):21053
pubmed: 33273499
Endocr Rev. 2008 Jun;29(4):403-40
pubmed: 18451259
Science. 2020 Oct 23;370(6515):
pubmed: 33093080
Nature. 2014 Mar 20;507(7492):376-380
pubmed: 24647000