Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance.
Bone resorption
Bone turnover
Cytokine
IL-17a
Inflammation
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
20
09
2021
revised:
09
12
2021
accepted:
21
12
2021
pubmed:
2
1
2022
medline:
3
5
2022
entrez:
1
1
2022
Statut:
ppublish
Résumé
Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of bone-resorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted Il17ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of Il17ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.
Identifiants
pubmed: 34973492
pii: S8756-3282(21)00476-2
doi: 10.1016/j.bone.2021.116310
pmc: PMC10084774
mid: NIHMS1771142
pii:
doi:
Substances chimiques
Cytokines
0
Il17a protein, mouse
0
Interleukin-17
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
116310Subventions
Organisme : BLRD VA
ID : I01 BX004708
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG064464
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Références
Biochimie. 2010 Apr;92(4):398-404
pubmed: 20045440
J Immunol. 2008 Aug 15;181(4):2799-805
pubmed: 18684971
Sci Rep. 2021 Aug 9;11(1):16155
pubmed: 34373550
Nat Med. 2012 Feb 19;18(3):405-12
pubmed: 22344299
J Dent Res. 2011 Feb;90(2):143-53
pubmed: 21135192
Lymphokine Cytokine Res. 1991 Apr;10(1-2):15-21
pubmed: 1873357
J Cell Physiol. 2016 Jun;231(6):1249-60
pubmed: 26491867
J Bone Miner Res. 2014 Sep;29(9):1981-92
pubmed: 24677326
J Periodontol. 2013 Nov;84(11):1627-37
pubmed: 23327689
Eur J Immunol. 2009 Oct;39(10):2831-9
pubmed: 19731364
Mol Med Rep. 2019 Jun;19(6):4743-4752
pubmed: 31059030
Cell Immunol. 2011;266(2):208-17
pubmed: 21074754
Nature. 1986 Feb 6-12;319(6053):516-8
pubmed: 3511389
J Bone Miner Res. 2006 Jan;21(1):67-77
pubmed: 16355275
J Cell Biochem. 2014 Aug;115(8):1412-9
pubmed: 24700654
Immunity. 2019 Apr 16;50(4):892-906
pubmed: 30995505
Prostate. 2015 Apr 1;75(5):449-62
pubmed: 25560177
PLoS One. 2020 Feb 13;15(2):e0228921
pubmed: 32053656
Arthritis Res Ther. 2010;12(1):R29
pubmed: 20167120
Am J Transl Res. 2017 Nov 15;9(11):5160-5168
pubmed: 29218113
Ann N Y Acad Sci. 2020 Mar;1463(1):45-59
pubmed: 31919867
Nature. 1997 Nov 13;390(6656):175-9
pubmed: 9367155
PLoS One. 2012;7(9):e44552
pubmed: 22970248
PLoS One. 2014 Jan 15;9(1):e85461
pubmed: 24454873
Exp Ther Med. 2019 Jul;18(1):517-522
pubmed: 31281442
Immunity. 2014 Dec 18;41(6):1052-63
pubmed: 25526314
Connect Tissue Res. 2018 Mar;59(2):99-107
pubmed: 28324674
Proc Natl Acad Sci U S A. 1990 Jun;87(12):4828-32
pubmed: 2191302
J Clin Invest. 2000 Dec;106(12):1481-8
pubmed: 11120755
Sci Rep. 2020 Mar 30;10(1):5692
pubmed: 32231224
J Bone Miner Res. 2012 Jul;27(7):1585-97
pubmed: 22431360
J Cell Biochem. 2012 Sep;113(9):2895-902
pubmed: 22511335
J Bone Miner Res. 2010 Jul;25(7):1468-86
pubmed: 20533309
Mediators Inflamm. 2019 Aug 14;2019:8659302
pubmed: 31485194
J Bone Miner Res. 2005 Sep;20(9):1659-68
pubmed: 16059637
Cytokine. 2008 Sep;43(3):402-7
pubmed: 18701318
J Clin Invest. 2005 Feb;115(2):282-90
pubmed: 15668736
Menopause. 2014 Jul;21(7):749-52
pubmed: 24253487