Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota.
Bone Biology
Bone disease
Dendritic cells
T cells
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 04 2020
01 04 2020
Historique:
received:
16
09
2019
accepted:
23
12
2019
pubmed:
10
1
2020
medline:
31
12
2020
entrez:
10
1
2020
Statut:
ppublish
Résumé
Parathyroid hormone (PTH) is a critical regulator of skeletal development that promotes both bone formation and bone resorption. Using microbiota depletion by wide-spectrum antibiotics and germ-free (GF) female mice, we showed that the microbiota was required for PTH to stimulate bone formation and increase bone mass. Microbiota depletion lowered butyrate levels, a metabolite responsible for gut-bone communication, while reestablishment of physiologic levels of butyrate restored PTH-induced anabolism. The permissive activity of butyrate was mediated by GPR43 signaling in dendritic cells and by GPR43-independent signaling in T cells. Butyrate was required for PTH to increase the number of bone marrow (BM) regulatory T cells (Tregs). Tregs stimulated production of the osteogenic Wnt ligand Wnt10b by BM CD8+ T cells, which activated Wnt-dependent bone formation. Together, these data highlight the role that butyrate produced by gut luminal microbiota plays in triggering regulatory pathways, which are critical for the anabolic action of PTH in bone.
Identifiants
pubmed: 31917685
pii: 133473
doi: 10.1172/JCI133473
pmc: PMC7108906
doi:
pii:
Substances chimiques
Butyrates
0
Ffar2 protein, mouse
0
Parathyroid Hormone
0
Receptors, G-Protein-Coupled
0
Wnt Proteins
0
Wnt10b protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1767-1781Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK112946
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR028009
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124821
Pays : United States
Organisme : BLRD VA
ID : I01 BX000105
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119229
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108842
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Free Radic Biol Med. 2013 Jul;60:195-200
pubmed: 23466556
Antioxid Redox Signal. 2014 Feb 10;20(5):818-30
pubmed: 23582008
J Bone Miner Res. 2013 Jan;28(1):2-17
pubmed: 23197339
Osteoporos Int. 2015 Dec;26(12):2785-91
pubmed: 26068297
Nature. 2013 Dec 19;504(7480):451-5
pubmed: 24226773
Bone. 2005 Apr;36(4):585-98
pubmed: 15777744
Arthritis Rheum. 2010 Aug;62(8):2328-38
pubmed: 20506516
Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):E725-33
pubmed: 22393015
Immunity. 2018 Dec 18;49(6):1116-1131.e7
pubmed: 30446387
J Bone Miner Res. 2017 Mar;32(3):522-535
pubmed: 27704638
J Endocrinol. 2005 Sep;186(3):549-57
pubmed: 16135674
Bone. 1995 Apr;16(4):477-84
pubmed: 7605709
Endocrinology. 1989 Mar;124(3):1247-53
pubmed: 2645113
Nat Commun. 2018 Jan 4;9(1):55
pubmed: 29302038
J Immunol. 2007 Jun 1;178(11):6715-9
pubmed: 17513716
Nat Rev Immunol. 2016 May;16(5):295-309
pubmed: 27087661
Nat Rev Immunol. 2019 Oct;19(10):614-625
pubmed: 31201377
Cell Metab. 2010 Feb 3;11(2):161-71
pubmed: 20142103
Gut. 2005 Aug;54(8):1182-93
pubmed: 15840688
Cell Metab. 2015 Nov 3;22(5):799-810
pubmed: 26456334
Endocrinology. 1991 Dec;129(6):3313-20
pubmed: 1954907
Nature. 1998 Mar 19;392(6673):245-52
pubmed: 9521319
Dis Model Mech. 2014 Aug;7(8):977-85
pubmed: 25056699
J Bone Miner Res. 2014 Jan;29(1):43-54
pubmed: 24357520
Cell Stem Cell. 2014 Jul 3;15(1):66-78
pubmed: 24726192
Ann Rheum Dis. 2009 May;68(5):744-50
pubmed: 18480308
EMBO Rep. 2018 Jan;19(1):156-171
pubmed: 29158349
Cell Metab. 2009 Sep;10(3):229-40
pubmed: 19723499
J Clin Endocrinol Metab. 2018 Nov 1;103(11):3993-4004
pubmed: 30060226
Biochem Biophys Res Commun. 2010 Nov 12;402(2):173-6
pubmed: 20920469
Science. 2013 Aug 2;341(6145):569-73
pubmed: 23828891
Sci Rep. 2017 Jul 18;7(1):5747
pubmed: 28720797
J Clin Invest. 2002 May;109(9):1173-82
pubmed: 11994406
Adv Nutr. 2015 Mar 13;6(2):206-13
pubmed: 25770259
Arthritis Rheum. 2007 Dec;56(12):4104-12
pubmed: 18050211
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7554-E7563
pubmed: 27821775
J Biol Chem. 2013 Jul 12;288(28):20122-34
pubmed: 23729679
Front Pharmacol. 2015 Sep 02;6:184
pubmed: 26388774
J Exp Med. 2005 Mar 7;201(5):723-35
pubmed: 15753206
Endocrinology. 2005 Nov;146(11):4577-83
pubmed: 16081646
Cold Spring Harb Perspect Med. 2018 Aug 1;8(8):
pubmed: 29358318
J Clin Invest. 2019 Jul 15;129(8):3018-3028
pubmed: 31305265
Trends Immunol. 2015 Jan;36(1):3-12
pubmed: 25248463
Blood. 2012 Nov 22;120(22):4352-62
pubmed: 22955916
Nature. 2009 Oct 29;461(7268):1282-6
pubmed: 19865172
J Bone Miner Res. 2002 Sep;17(9):1570-8
pubmed: 12211426
Immunity. 2009 May;30(5):636-45
pubmed: 19464986
J Bone Miner Res. 2010 Jul;25(7):1468-86
pubmed: 20533309
J Bone Miner Res. 2000 May;15(5):879-84
pubmed: 10804017
J Nutr. 2003 Nov;133(11):3523-8
pubmed: 14608068
J Bone Miner Res. 2012 Jun;27(6):1357-67
pubmed: 22407806
Biochem Biophys Res Commun. 2007 Jun 15;357(4):1046-52
pubmed: 17462597
Nature. 2011 Jun 08;474(7350):216-9
pubmed: 21654805
J Mol Histol. 2007 Aug;38(4):261-9
pubmed: 17549589
Bone. 2005 Aug;37(2):148-58
pubmed: 15946907
Bone. 2007 Jun;40(6):1434-46
pubmed: 17517365
J Bone Miner Res. 2015 Apr;30(4):695-705
pubmed: 25359628
J Cell Physiol. 2015 Mar;230(3):667-79
pubmed: 25187507
Biochem Biophys Res Commun. 2003 Apr 18;303(4):1047-52
pubmed: 12684041
Diabetes. 2013 Feb;62(2):551-60
pubmed: 23099863
Immunity. 2014 Jan 16;40(1):128-39
pubmed: 24412617
J Bone Miner Res. 2010 Apr;25(4):819-29
pubmed: 19821778
Nature. 2013 Dec 19;504(7480):446-50
pubmed: 24226770
Trends Endocrinol Metab. 2004 Mar;15(2):60-5
pubmed: 15036251
Curr Protoc Immunol. 2001 May;Chapter 3:Unit 3.19
pubmed: 18432783