Skeleton-secreted PDGF-BB mediates arterial stiffening.
Bone Biology
Vascular Biology
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:
15 10 2021
15 10 2021
Historique:
received:
23
12
2020
accepted:
24
08
2021
pubmed:
27
8
2021
medline:
15
12
2021
entrez:
26
8
2021
Statut:
ppublish
Résumé
Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-secreted platelet-derived growth factor-BB (PDGF-BB) as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, respectively, had higher serum PDGF-BB and developed bone loss and arterial stiffening. Bone/bone marrow preosteoclasts in aged mice and HFD mice secrete an excessive amount of PDGF-BB, contributing to the elevated PDGF-BB in blood circulation. Conditioned medium prepared from preosteoclasts stimulated proliferation and migration of the vascular smooth muscle cells. Conditional transgenic mice, in which PDGF-BB is overexpressed in preosteoclasts, had 3-fold higher serum PDGF-BB concentration and developed simultaneous bone loss and arterial stiffening spontaneously at a young age. Conversely, in conditional knockout mice, in which PDGF-BB is deleted selectively in preosteoclasts, HFD did not affect serum PDGF-BB concentration; as a result, HFD-induced bone loss and arterial stiffening were attenuated. These studies confirm that preosteoclasts are a main source of excessive PDGF-BB in blood circulation during aging and metabolic stress and establish the role of skeleton-derived PDGF-BB as an important mediator of vascular stiffening.
Identifiants
pubmed: 34437300
pii: e147116
doi: 10.1172/JCI147116
pmc: PMC8516464
doi:
pii:
Substances chimiques
Becaplermin
1B56C968OA
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL148112
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG068997
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG066603
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG076783
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG072090
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG068226
Pays : United States
Commentaires et corrections
Type : CommentIn
Références
J Bone Miner Res. 2005 Nov;20(11):1912-20
pubmed: 16234963
J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S109-11
pubmed: 16565231
Bonekey Rep. 2013 Dec 04;2:449
pubmed: 24422142
Circulation. 2012 Jun 5;125(22):2772-81
pubmed: 22665885
Respir Res. 2018 Jun 19;19(1):120
pubmed: 29921306
Eur Heart J. 2015 Dec 21;36(48):3392-403
pubmed: 26543043
Front Genet. 2015 Mar 30;6:112
pubmed: 25926844
Endocr Pract. 2012 Sep-Oct;18(5):758-62
pubmed: 22784851
Genes Dev. 2008 May 15;22(10):1276-312
pubmed: 18483217
Cytokine Growth Factor Rev. 2004 Aug;15(4):255-73
pubmed: 15207816
Atherosclerosis. 2010 Mar;209(1):283-9
pubmed: 19819456
Can J Cardiol. 2016 May;32(5):634-41
pubmed: 26948035
J Appl Physiol (1985). 2008 Nov;105(5):1632-42
pubmed: 18719233
Nat Med. 2011 Apr;17(4):430-1
pubmed: 21475237
Circ Res. 2007 Mar 16;100(5):607-21
pubmed: 17363707
Clin Exp Pharmacol Physiol. 1993 May;20(5):324-6
pubmed: 8324917
Mol Cells. 2017 Oct;40(10):706-713
pubmed: 29047262
Hypertension. 2007 Jul;50(1):219-27
pubmed: 17452499
Annu Rev Physiol. 2012;74:87-105
pubmed: 22077214
Circulation. 2002 Jun 18;105(24):2893-8
pubmed: 12070119
Nat Commun. 2021 Mar 23;12(1):1832
pubmed: 33758201
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1908-13
pubmed: 21245329
J Intern Med. 2017 May;281(5):471-482
pubmed: 28345303
Nat Rev Rheumatol. 2011 Apr;7(4):235-43
pubmed: 21386794
J Vasc Surg. 2004 Dec;40(6):1199-207
pubmed: 15622375
Front Cardiovasc Med. 2018 Nov 23;5:172
pubmed: 30533416
J Am Heart Assoc. 2014 Apr 10;3(2):e000599
pubmed: 24721796
J Dent Res. 2013 Oct;92(10):860-7
pubmed: 23906603
Hypertension. 2016 Sep;68(3):775-84
pubmed: 27432859
Hypertension. 2013 Dec;62(6):1105-10
pubmed: 24060894
Arch Biochem Biophys. 2014 Sep 15;558:70-8
pubmed: 24976175
Front Physiol. 2017 Jun 30;8:456
pubmed: 28713285
Ageing Res Rev. 2017 Aug;37:94-116
pubmed: 28579130
Circulation. 2006 Feb 7;113(5):657-63
pubmed: 16461838
Genes Dev. 1994 Aug 15;8(16):1875-87
pubmed: 7958863
J Invest Dermatol. 1989 Feb;92(2):301-3
pubmed: 2918236
Trends Endocrinol Metab. 2019 Sep;30(9):646-657
pubmed: 31279666
J Cell Biochem. 2016 Aug;117(8):1753-6
pubmed: 27019318
Mod Rheumatol. 2008;18(3):220-7
pubmed: 18425565
Pulse (Basel). 2013 Apr;1(1):14-28
pubmed: 26587425
J Am Coll Cardiol. 2010 Nov 16;56(21):1752-9
pubmed: 21070928
J Am Coll Cardiol. 2007 Jul 3;50(1):1-13
pubmed: 17601538
Am J Hypertens. 1998 Oct;11(10):1239-43
pubmed: 9799041
Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2069-75
pubmed: 19797706
Nat Med. 2014 Nov;20(11):1270-8
pubmed: 25282358
Endocr Rev. 2011 Feb;32(1):31-63
pubmed: 20851921
J Exp Med. 1988 Jan 1;167(1):163-74
pubmed: 3335829
J Cell Physiol. 2010 Oct;225(1):115-22
pubmed: 20648629
Atherosclerosis. 1991 Jul;89(1):11-24
pubmed: 1772469
Heart. 2016 Nov 1;102(21):1710-1715
pubmed: 27406839
Arterioscler Thromb Vasc Biol. 2020 May;40(5):1068-1077
pubmed: 32268787
Cytokine Growth Factor Rev. 2004 Aug;15(4):237-54
pubmed: 15207815
Clin Cases Miner Bone Metab. 2008 Jan;5(1):19-34
pubmed: 22460842
Hypertension. 1991 Nov;18(5 Suppl):III93-9
pubmed: 1657776
Neurosurgery. 2010 Apr;66(4):728-35; discussion 735
pubmed: 20305494
J Bone Miner Res. 2006 Apr;21(4):549-55
pubmed: 16598375
Circ Res. 2012 Apr 13;110(8):1097-108
pubmed: 22499900
J Cell Physiol. 2018 Apr;233(4):2804-2814
pubmed: 28467642
Circ Res. 2016 Mar 18;118(6):935-943
pubmed: 26879229
Atherosclerosis. 2011 Feb;214(2):288-94
pubmed: 21129745
Bone Res. 2018 Jul 18;6:22
pubmed: 30038821
Nat Commun. 2017 Nov 3;8(1):1312
pubmed: 29101351
Curr Osteoporos Rep. 2015 Aug;13(4):206-15
pubmed: 25947259
Nat Rev Endocrinol. 2012 Sep;8(9):529-43
pubmed: 22473330
J Intern Med. 1991 Oct;230(4):313-7
pubmed: 1919424
J Am Heart Assoc. 2015 Feb 25;4(3):e001744
pubmed: 25716945
Nat Commun. 2015 Jul 17;6:7770
pubmed: 26183159
Exp Cell Res. 2016 Dec 10;349(2):282-290
pubmed: 27816607
JACC Cardiovasc Imaging. 2012 Apr;5(4):367-9
pubmed: 22498325
Clin Exp Pharmacol Physiol. 2015 Dec;42(12):1221-4
pubmed: 26277708
Clin Exp Pharmacol Physiol. 2009 Aug;36(8):739-47
pubmed: 19473339
Anat Cell Biol. 2019 Jun;52(2):109-114
pubmed: 31338225
Int J Mol Sci. 2019 Nov 14;20(22):
pubmed: 31739395
Science. 1986 Apr 4;232(4746):87-90
pubmed: 3485309
Ann N Y Acad Sci. 2006 Apr;1068:327-33
pubmed: 16831933
Hypertension. 2006 Mar;47(3):365-70
pubmed: 16432047
J Musculoskelet Neuronal Interact. 2008 Jul-Sep;8(3):204-16
pubmed: 18799853
Stroke. 2009 Feb;40(2):591-6
pubmed: 19095985
J Gastroenterol. 1997 Aug;32(4):496-501
pubmed: 9250897
Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H49-H59
pubmed: 31002285
Endocr Rev. 2000 Apr;21(2):115-37
pubmed: 10782361
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1423-30
pubmed: 16601233
JCI Insight. 2020 Apr 23;5(8):
pubmed: 32208385
Physiol Rev. 2017 Oct 1;97(4):1555-1617
pubmed: 28954852
Calcif Tissue Int. 2003 Jul;73(1):15-20
pubmed: 14506949
J Bone Miner Res. 2001 Jan;16(1):182-8
pubmed: 11149483
Integr Blood Press Control. 2014 May 23;7:29-34
pubmed: 24910511