An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis.
Animals
Bone Regeneration
Cell Line
Cells, Cultured
Cytokines
/ metabolism
Enzyme Inhibitors
/ administration & dosage
Female
Forkhead Transcription Factors
/ metabolism
Gingiva
/ metabolism
Humans
Hydrogels
/ administration & dosage
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Hypoxia-Inducible Factor-Proline Dioxygenases
/ antagonists & inhibitors
Male
Mice
Mice, Inbred C57BL
Osteogenesis
Periodontitis
/ drug therapy
T-Lymphocytes, Regulatory
/ immunology
1,4-dihydrophenonthrolin-4-one-3-carboxylic acid
AMD3100
T regulatory cells
hypoxia-inducible factor 1α
osteogenesis
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
17
05
2020
revised:
29
07
2020
accepted:
31
07
2020
pubmed:
20
8
2020
medline:
1
5
2021
entrez:
20
8
2020
Statut:
ppublish
Résumé
The hypoxia-inducible factor 1α (HIF-1α) is critically involved in tissue regeneration. Hence, the pharmacological prevention of HIF-1α degradation by prolyl hydroxylase (PHD) under normoxic conditions is emerging as a promising option in regenerative medicine. Using a mouse model of ligature-induced periodontitis and resolution, we tested the ability of an injectable hydrogel-formulated PHD inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA/hydrogel), to promote regeneration of alveolar bone lost owing to experimental periodontitis. Mice injected subcutaneously with 1,4-DPCA/hydrogel at the onset of periodontitis resolution displayed significantly increased gingival HIF-1α protein levels and bone regeneration, as compared to mice treated with vehicle control. The 1,4-DPCA/hydrogel-induced increase in bone regeneration was associated with elevated expression of osteogenic genes, decreased expression of pro-inflammatory cytokine genes, and increased abundance of FOXP3
Identifiants
pubmed: 32812255
doi: 10.1096/fj.202001248R
pmc: PMC7722135
mid: NIHMS1630049
doi:
Substances chimiques
Cytokines
0
Enzyme Inhibitors
0
Forkhead Transcription Factors
0
Foxp3 protein, mouse
0
Hif1a protein, mouse
0
Hydrogels
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Hypoxia-Inducible Factor-Proline Dioxygenases
EC 1.14.11.29
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13726-13740Subventions
Organisme : NIDCR NIH HHS
ID : R37 DE026152
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028561
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE021104
Pays : United States
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
J Dent Res. 2014 Nov;93(11):1045-53
pubmed: 25261053
J Periodontol. 2015 Feb;86(2 Suppl):S153-6
pubmed: 25317603
Stem Cells Int. 2018 Jul 30;2018:2495848
pubmed: 30154861
J Clin Periodontol. 2008 Sep;35(8 Suppl):106-16
pubmed: 18724845
Nat Rev Microbiol. 2018 Dec;16(12):745-759
pubmed: 30301974
Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):686-91
pubmed: 18184809
Cell Metab. 2018 Feb 6;27(2):281-298
pubmed: 29129785
J Dent Res. 2015 Jan;94(1):148-56
pubmed: 25389003
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):E2784-93
pubmed: 22988108
Adv Wound Care (New Rochelle). 2014 May 1;3(5):390-399
pubmed: 24804159
J Periodontol. 2015 Feb;86(2 Suppl):S134-52
pubmed: 25644297
J Periodontal Res. 2006 Dec;41(6):547-53
pubmed: 17076780
Periodontol 2000. 2015 Jun;68(1):182-216
pubmed: 25867987
J Cell Biochem. 2016 Feb;117(2):267-78
pubmed: 26206147
Int Dent J. 2013 Dec;63(6):306-11
pubmed: 24716244
J Periodontol. 2012 Oct;83(10):1279-87
pubmed: 22324467
Nat Med. 2011 Nov 20;17(12):1594-601
pubmed: 22101767
J Clin Periodontol. 2017 Mar;44 Suppl 18:S94-S105
pubmed: 28266116
J Biol Chem. 1996 Dec 13;271(50):32253-9
pubmed: 8943284
Nat Rev Dis Primers. 2017 Jun 22;3:17038
pubmed: 28805207
Trends Mol Med. 2018 Dec;24(12):1021-1035
pubmed: 30391126
Nat Immunol. 2019 Jan;20(1):40-49
pubmed: 30455459
J Immunol Methods. 2013 Aug 30;394(1-2):49-54
pubmed: 23672778
J Dent Res. 2013 Aug;92(8):709-15
pubmed: 23735585
Nat Med. 1998 Jan;4(1):72-7
pubmed: 9427609
Nat Commun. 2015 Sep 16;6:8272
pubmed: 26374165
BMJ. 2014 Apr 10;348:g2645
pubmed: 24721751
Nat Rev Immunol. 2011 Feb;11(2):119-30
pubmed: 21267013
Periodontol 2000. 2010 Jun;53:28-44
pubmed: 20403103
J Exp Med. 2003 Nov 3;198(9):1391-402
pubmed: 14597738
Sci Transl Med. 2015 Sep 30;7(307):307ra155
pubmed: 26424570
Chem Commun (Camb). 2005 Nov 21;(43):5438-40
pubmed: 16261239
Front Pharmacol. 2015 Sep 02;6:184
pubmed: 26388774
Cell. 2008 May 30;133(5):775-87
pubmed: 18510923
J Clin Invest. 2009 Oct;119(10):2898-913
pubmed: 19770521
Nat Immunol. 2017 Oct;18(10):1160-1172
pubmed: 28783152
Periodontol 2000. 2019 Feb;79(1):15-21
pubmed: 30887589
J Periodontol. 2015 May;86(5):611-22
pubmed: 25688694
J Leukoc Biol. 2014 Nov;96(5):809-20
pubmed: 25082151
Cell. 2015 Aug 27;162(5):1078-89
pubmed: 26317471
J Bone Miner Res. 2009 Aug;24(8):1347-53
pubmed: 19558314
J Clin Periodontol. 2011 Mar;38 Suppl 11:114-8
pubmed: 21323708
Trends Mol Med. 2017 Nov;23(11):1024-1036
pubmed: 28988849
Nat Rev Immunol. 2015 Jan;15(1):30-44
pubmed: 25534621
J Orthop Translat. 2017 Mar 29;9:19-27
pubmed: 29662796
J Biol Chem. 2020 May 22;295(21):7261-7273
pubmed: 32280065
FASEB J. 2012 Apr;26(4):1423-30
pubmed: 22179526
J Biol Chem. 2007 Sep 14;282(37):26746-53
pubmed: 17626014
J Periodontal Res. 2010 Feb;45(1):60-70
pubmed: 19453851
Adv Drug Deliv Rev. 2018 Apr;129:254-261
pubmed: 29524586
Immunity. 2018 Dec 18;49(6):1116-1131.e7
pubmed: 30446387
Front Immunol. 2018 Mar 23;9:585
pubmed: 29662491
Sci Transl Med. 2016 Aug 17;8(352):352ra108
pubmed: 27535619
Nat Rev Immunol. 2008 May;8(5):349-61
pubmed: 18437155
Sci Transl Med. 2018 Oct 17;10(463):
pubmed: 30333238
Orthod Craniofac Res. 2005 Nov;8(4):285-91
pubmed: 16238609
Breast Cancer Res. 2011 Apr 26;13(2):R47
pubmed: 21521526
Apoptosis. 2019 Feb;24(1-2):108-118
pubmed: 30610504
Mol Cancer Ther. 2012 Mar;11(3):538-48
pubmed: 22357635
Sci Transl Med. 2015 Jun 3;7(290):290ra92
pubmed: 26041709
J Clin Invest. 2019 Jun 4;129(9):3640-3656
pubmed: 31162141
J Periodontol. 2011 Jan;82(1):136-41
pubmed: 21043802
Cancer Res. 2004 Nov 15;64(22):8451-5
pubmed: 15548717
Periodontol 2000. 2011 Jun;56(1):188-208
pubmed: 21501244
J Biomed Mater Res A. 2013 Dec;101(12):3599-606
pubmed: 23766241
J Periodontal Res. 1999 Oct;34(7):420-4
pubmed: 10685371
Periodontol 2000. 2011 Feb;55(1):87-103
pubmed: 21134230