Differential expression of the inflammatory ciita gene may be accompanied by altered bone properties in intact sex steroid-deficient female rats.
BMD
Biomechanical testing
Bone
Ciita
Inflammation
Ovariectomy
Rat
micro-CT
Journal
BMC research notes
ISSN: 1756-0500
Titre abrégé: BMC Res Notes
Pays: England
ID NLM: 101462768
Informations de publication
Date de publication:
19 Dec 2023
19 Dec 2023
Historique:
received:
12
04
2023
accepted:
28
09
2023
medline:
20
12
2023
pubmed:
20
12
2023
entrez:
20
12
2023
Statut:
epublish
Résumé
The class II transactivator (CIITA), encoded by the CIITA gene, controls expression of immune response regulators, which affect bone homeostasis. Previously, we investigated a functional CIITA polymorphism in elderly women. Women carrying the allele associated with lower CIITA levels displayed higher bone mineral density (BMD), but also higher bone loss. The present exploratory study in a rat model sought to investigate effects of differential expression of Ciita on bone structural integrity and strength. Two strains DA (normal-to-high expression) and DA.VRA4 (lower expression) underwent ovariectomy (OVX) or sham-surgery at ~ 14-weeks of age (DA OVX n = 8, sham n = 4; DA.VRA4 OVX n = 10, sham n = 2). After 16-weeks, femoral BMD and bone mineral content (BMC) were measured and morphometry and biomechanical testing performed. In DA.VRA4 rats, BMD/BMC, cross-sectional area and biomechanical properties were lower. Ciita expression was accompanied by OVX-induced changes to cross-sectional area and femoral shaft strength; DA rats had lower maximum load-to-fracture. Thus, while lower Ciita expression associated with lower bone mass, OVX induced changes to structural and mechanical bone properties were less pronounced. The data tentatively suggests association between Ciita expression and structural and mechanical bone properties, and a possible role in bone changes resulting from estrogen deficiency.
Identifiants
pubmed: 38115045
doi: 10.1186/s13104-023-06543-4
pii: 10.1186/s13104-023-06543-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
372Informations de copyright
© 2023. The Author(s).
Références
Mori G, D’Amelio P, Faccio R, Brunetti G. The interplay between the bone and the immune system. Clin Dev Immunol. 2013;2013:720504.
doi: 10.1155/2013/720504
pubmed: 23935650
pmcid: 3725924
Cenci S, Toraldo G, Weitzmann MN, Roggia C, Gao Y, Qian WP, et al. Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci U S A. 2003;100(18):10405–10.
doi: 10.1073/pnas.1533207100
pubmed: 12923292
pmcid: 193574
Roggia C, Tamone C, Cenci S, Pacifici R, Isaia GC. Role of TNF-alpha producing T-cells in bone loss induced by estrogen deficiency. Minerva Med. 2004;95(2):125–32.
pubmed: 15272247
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761–7.
doi: 10.1016/S0140-6736(02)08657-9
pubmed: 12049882
Nakamura MC. CIITA: a master regulator of adaptive immunity shows its innate side in the bone. J Bone Miner Res. 2014;29(2):287–9.
doi: 10.1002/jbmr.2161
pubmed: 24343972
Benasciutti E, Mariani E, Oliva L, Scolari M, Perilli E, Barras E, et al. MHC class II transactivator is an in vivo Regulator of Osteoclast differentiation and bone homeostasis co-opted from adaptive immunity. J Bone Miner Res. 2014;29(2):290–303.
doi: 10.1002/jbmr.2090
pubmed: 24038328
Swanberg M, McGuigan FE, Ivaska KK, Gerdhem P, Åkesson K. Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women. PLoS ONE. 2012;7(10):e47964–e.
doi: 10.1371/journal.pone.0047964
pubmed: 23133532
pmcid: 3485004
Berglundh S, Malmgren L, Luthman H, McGuigan F, Akesson K. C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort. Osteoporos Int. 2015;26(2):727–35.
doi: 10.1007/s00198-014-2951-7
pubmed: 25410434
Hochmeister S, Aeinehband S, Dorris C, Berglund R, Haindl MT, Velikic V, et al. Effect of vitamin D on experimental autoimmune neuroinflammation is dependent on haplotypes comprising naturally occurring allelic variants of CIITA (Mhc2ta). Front Neurol. 2020;11:600401.
doi: 10.3389/fneur.2020.600401
pubmed: 33304315
pmcid: 7693436
Harnesk K, Swanberg M, Ockinger J, Diez M, Lidman O, Wallstrom E, et al. Vra4 congenic rats with allelic differences in the class II transactivator gene display altered susceptibility to experimental autoimmune encephalomyelitis. J Immunol. 2008;180(5):3289–96.
doi: 10.4049/jimmunol.180.5.3289
pubmed: 18292553
Jimenez-Ferrer I, Jewett M, Tontanahal A, Romero-Ramos M, Swanberg M. Allelic difference in Mhc2ta confers altered microglial activation and susceptibility to α-synuclein-induced dopaminergic neurodegeneration. Neurobiol Dis. 2017;106:279–90.
doi: 10.1016/j.nbd.2017.07.016
pubmed: 28736195
Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, et al. MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet. 2005;37(5):486–94.
doi: 10.1038/ng1544
pubmed: 15821736
Kharode YP, Sharp MC, Bodine PV. Utility of the ovariectomized rat as a model for human osteoporosis in drug discovery. Methods Mol Biol. 2008;455:111–24.
doi: 10.1007/978-1-59745-104-8_8
pubmed: 18463814
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82.
doi: 10.1038/nmeth.2019
pubmed: 22743772
Doube M, Kłosowski MM, Arganda-Carreras I, Cordelières FP, Dougherty RP, Jackson JS, et al. BoneJ: free and extensible bone image analysis in ImageJ. Bone. 2010;47(6):1076–9.
doi: 10.1016/j.bone.2010.08.023
pubmed: 20817052
pmcid: 3193171
Kim JH, Kim K, Youn BU, Jin HM, Kim N. MHC class II transactivator negatively regulates RANKL-mediated osteoclast differentiation by downregulating NFATc1 and OSCAR. Cell Signal. 2010;22(9):1341–9.
doi: 10.1016/j.cellsig.2010.05.001
pubmed: 20466061
Adamski J, Ma Z, Nozell S, Benveniste EN. 17beta-Estradiol inhibits class II major histocompatibility complex (MHC) expression: influence on histone modifications and cbp recruitment to the class II MHC promoter. Mol Endocrinol. 2004;18(8):1963–74.
doi: 10.1210/me.2004-0098
pubmed: 15143155
Mostafa AA, Codner D, Hirasawa K, Komatsu Y, Young MN, Steimle V, et al. Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells. PLoS ONE. 2014;9(1):e87377.
doi: 10.1371/journal.pone.0087377
pubmed: 24475282
pmcid: 3903652