Comparison of the effects of high dietary iron levels on bone microarchitecture responses in the mouse strains 129/Sv and C57BL/6J.
129/Sv
Bone loss
C57BL/6J
Iron-rich diet
Mouse strains
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 Feb 2024
28 Feb 2024
Historique:
received:
11
10
2023
accepted:
22
02
2024
medline:
29
2
2024
pubmed:
29
2
2024
entrez:
28
2
2024
Statut:
epublish
Résumé
Iron is an essential nutrient for all living organisms. Both iron deficiency and excess can be harmful. Bone, a highly metabolic active organ, is particularly sensitive to fluctuations in iron levels. In this study, we investigated the effects of dietary iron overload on bone homeostasis with a specific focus on two frequently utilized mouse strains: 129/Sv and C57BL/6J. Our findings revealed that after 6 weeks on an iron-rich diet, 129/Sv mice exhibited a decrease in trabecular and cortical bone density in both vertebral and femoral bones, which was linked to reduced bone turnover. In contrast, there was no evidence of bone changes associated with iron overload in age-matched C57BL/6J mice. Interestingly, 129/Sv mice exposed to an iron-rich diet during their prenatal development were protected from iron-induced bone loss, suggesting the presence of potential adaptive mechanisms. Overall, our study underscores the critical role of genetic background in modulating the effects of iron overload on bone health. This should be considered when studying effects of iron on bone.
Identifiants
pubmed: 38418857
doi: 10.1038/s41598-024-55303-2
pii: 10.1038/s41598-024-55303-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4887Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : LE 4894/1-1
Organisme : Deutsche Forschungsgemeinschaft
ID : Ferros FOR5146
Informations de copyright
© 2024. The Author(s).
Références
Hentze, M. W., Muckenthaler, M. U., Galy, B. & Camaschella, C. Two to tango: regulation of Mammalian iron metabolism. Cell 142, 24–38. https://doi.org/10.1016/j.cell.2010.06.028 (2010).
doi: 10.1016/j.cell.2010.06.028
pubmed: 20603012
Dev, S. & Babitt, J. L. Overview of iron metabolism in health and disease. Hemodial Int. 21(Suppl 1), S6–S20. https://doi.org/10.1111/hdi.12542 (2017).
doi: 10.1111/hdi.12542
pubmed: 28296010
pmcid: 5977983
Wang, C. Y. & Babitt, J. L. Liver iron sensing and body iron homeostasis. Blood 133, 18–29. https://doi.org/10.1182/blood-2018-06-815894 (2019).
doi: 10.1182/blood-2018-06-815894
pubmed: 30401708
pmcid: 6318427
Ledesma-Colunga, M. G. et al. Shaping the bone through iron and iron-related proteins. Semin. Hematol. 58, 188–200. https://doi.org/10.1053/j.seminhematol.2021.06.002 (2021).
doi: 10.1053/j.seminhematol.2021.06.002
pubmed: 34389111
Kim, B. J. et al. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: A 3-year retrospective longitudinal study. J. Bone Miner. Res. 27, 2279–2290. https://doi.org/10.1002/jbmr.1692 (2012).
doi: 10.1002/jbmr.1692
pubmed: 22729843
Weidner, H. et al. Myelodysplastic syndromes and bone loss in mice and men. Leukemia 31, 1003–1007. https://doi.org/10.1038/leu.2017.7 (2017).
doi: 10.1038/leu.2017.7
pubmed: 28074069
Guggenbuhl, P. et al. Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporos. Int. 16, 1809–1814 (2005).
doi: 10.1007/s00198-005-1934-0
pubmed: 15928800
Vogiatzi, M. G. et al. Bone disease in thalassemia: A frequent and still unresolved problem. J. Bone Miner. Res. 24, 543–557. https://doi.org/10.1359/jbmr.080505 (2009).
doi: 10.1359/jbmr.080505
pubmed: 18505376
Li, G. et al. Hepcidin deficiency causes bone loss through interfering with the canonical Wnt/beta-catenin pathway via Forkhead box O3a. J. Orthop. Transl. 23, 67–76. https://doi.org/10.1016/j.jot.2020.03.012 (2020).
doi: 10.1016/j.jot.2020.03.012
Ledesma-Colunga, M. G. et al. Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice. Bone 137, 115400. https://doi.org/10.1016/j.bone.2020.115400 (2020).
doi: 10.1016/j.bone.2020.115400
pubmed: 32380257
Doyard, M. et al. Decreased bone formation explains osteoporosis in a genetic mouse model of hemochromatosiss. PLoS ONE 11, e0148292. https://doi.org/10.1371/journal.pone.0148292 (2016).
doi: 10.1371/journal.pone.0148292
pubmed: 26829642
pmcid: 4734777
Wagner, A. et al. Despite genetic iron overload, Hfe-hemochromatosis mice do not show bone loss. JBMR Plus 3, e10206. https://doi.org/10.1002/jbm4.10206 (2019).
doi: 10.1002/jbm4.10206
pubmed: 31667458
pmcid: 6808227
Rauner, M. et al. Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling. Nat. Metab. 1, 111–124. https://doi.org/10.1038/s42255-018-0005-8 (2019).
doi: 10.1038/s42255-018-0005-8
pubmed: 30886999
pmcid: 6420074
Balogh, E. et al. Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin. Biochim. Biophys. Acta 1640–1649, 2016. https://doi.org/10.1016/j.bbadis.2016.06.003 (1862).
doi: 10.1016/j.bbadis.2016.06.003
Jing, X. et al. Icariin protects against iron overload-induced bone loss via suppressing oxidative stress. J. Cell Physiol. 234, 10123–10137. https://doi.org/10.1002/jcp.27678 (2019).
doi: 10.1002/jcp.27678
pubmed: 30387158
Ahmad, N. S., Khalid, B. A., Luke, D. A. & Ima Nirwana, S. Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone. Clin. Exp. Pharmacol. Physiol. 32, 761–770. https://doi.org/10.1111/j.1440-1681.2005.04264.x (2005).
doi: 10.1111/j.1440-1681.2005.04264.x
pubmed: 16173934
Tsay, J. et al. Bone loss caused by iron overload in a murine model: Importance of oxidative stress. Blood 116, 2582–2589. https://doi.org/10.1182/blood-2009-12-260083 (2010).
doi: 10.1182/blood-2009-12-260083
pubmed: 20554970
pmcid: 2953890
Xiao, W. et al. Iron overload increases osteoclastogenesis and aggravates the effects of ovariectomy on bone mass. J. Endocrinol. 226, 121–134. https://doi.org/10.1530/JOE-14-0657 (2015).
doi: 10.1530/JOE-14-0657
pubmed: 26116610
Simao, M. et al. Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis. PLoS ONE 13, e0207441. https://doi.org/10.1371/journal.pone.0207441 (2018).
doi: 10.1371/journal.pone.0207441
pubmed: 30427936
pmcid: 6241130
Donovan, A. et al. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 1, 191–200. https://doi.org/10.1016/j.cmet.2005.01.003 (2005).
doi: 10.1016/j.cmet.2005.01.003
pubmed: 16054062
Huang, F. W., Pinkus, J. L., Pinkus, G. S., Fleming, M. D. & Andrews, N. C. A mouse model of juvenile hemochromatosis. J. Clin. Invest. 115, 2187–2191. https://doi.org/10.1172/JCI25049 (2005).
doi: 10.1172/JCI25049
pubmed: 16075059
pmcid: 1180543
Roetto, A. et al. Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues. Blood 115, 3382–3389. https://doi.org/10.1182/blood-2009-09-240960 (2010).
doi: 10.1182/blood-2009-09-240960
pubmed: 20179178
Dempster, D. W. et al. Standardized nomenclature, symbols, and units for bone histomorphometry: A 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J. Bone Miner. Res. 28, 2–17. https://doi.org/10.1002/jbmr.1805 (2013).
doi: 10.1002/jbmr.1805
pubmed: 23197339
Torrance, J. D. & Bothwell, T. H. A simple technique for measuring storage iron concentrations in formalinised liver samples. S. Afr. J. Med. Sci. 33, 9–11 (1968).
pubmed: 5676884
Daba, A., Gkouvatsos, K., Sebastiani, G. & Pantopoulos, K. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: Compartmentalization is critical for iron sensing. J. Mol. Med. 91, 95–102. https://doi.org/10.1007/s00109-012-0937-5 (2013).
doi: 10.1007/s00109-012-0937-5
pubmed: 22847740
Almeida, A. & Roberts, I. Bone involvement in sickle cell disease. Br. J. Haematol. 129, 482–490. https://doi.org/10.1111/j.1365-2141.2005.05476.x (2005).
doi: 10.1111/j.1365-2141.2005.05476.x
pubmed: 15877730
Jia, P. et al. Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species. J. Orthop. Res. 30, 1843–1852. https://doi.org/10.1002/jor.22133 (2012).
doi: 10.1002/jor.22133
pubmed: 22570238
Corradini, E. et al. Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology 54, 273–284. https://doi.org/10.1002/hep.24359 (2011).
doi: 10.1002/hep.24359
pubmed: 21488083
Rishi, G., Secondes, E. S. & Nathan Subramaniam, V. Hemochromatosis: Evaluation of the dietary iron model and regulation of hepcidin. Biochim. Biophys. Acta Mol. Basis Dis. 2550–2556, 2018. https://doi.org/10.1016/j.bbadis.2018.05.005 (1864).
doi: 10.1016/j.bbadis.2018.05.005
Bryant, C. D. The blessings and curses of C57BL/6 substrains in mouse genetic studies. Ann. N. Y. Acad. Sci. 1245, 31–33. https://doi.org/10.1111/j.1749-6632.2011.06325.x (2011).
doi: 10.1111/j.1749-6632.2011.06325.x
pubmed: 22211972
pmcid: 4944652
Enns, C. A. et al. Increased iron loading induces Bmp6 expression in the non-parenchymal cells of the liver independent of the BMP-signaling pathway. PLoS ONE 8, e60534. https://doi.org/10.1371/journal.pone.0060534 (2013).
doi: 10.1371/journal.pone.0060534
pubmed: 23565256
pmcid: 3615098
Nam, H. & Knutson, M. D. Effect of dietary iron deficiency and overload on the expression of ZIP metal-ion transporters in rat liver. Biometals 25, 115–124. https://doi.org/10.1007/s10534-011-9487-5 (2012).
doi: 10.1007/s10534-011-9487-5
pubmed: 21826460
Saha, P. et al. Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains. Physiol. Rep. 8, e14441. https://doi.org/10.14814/phy2.14441 (2020).
doi: 10.14814/phy2.14441
pubmed: 32385968
pmcid: 7210116
Dupic, F. et al. Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice. Gut 51, 648–653. https://doi.org/10.1136/gut.51.5.648 (2002).
doi: 10.1136/gut.51.5.648
pubmed: 12377801
pmcid: 1773425
Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D. & Andrews, N. C. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94, 9–11 (1999).
doi: 10.1182/blood.V94.1.9.413a43_9_11
pubmed: 10381492
Ward, P. P., Mendoza-Meneses, M., Cunningham, G. A. & Conneely, O. M. Iron status in mice carrying a targeted disruption of lactoferrin. Mol. Cell Biol. 23, 178–185. https://doi.org/10.1128/MCB.23.1.178-185.2003 (2003).
doi: 10.1128/MCB.23.1.178-185.2003
pubmed: 12482971
pmcid: 140657
Whitfield, J. B. et al. Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins. Am. J. Hum. Genet. 66, 1246–1258. https://doi.org/10.1086/302862 (2000).
doi: 10.1086/302862
pubmed: 10739755
pmcid: 1288192
Clothier, B. et al. Genetic variation of basal iron status, ferritin and iron regulatory protein in mice: Potential for modulation of oxidative stress. Biochem. Pharmacol. 59, 115–122. https://doi.org/10.1016/s0006-2952(99)00306-8 (2000).
doi: 10.1016/s0006-2952(99)00306-8
pubmed: 10810445
Leboeuf, R. C., Tolson, D. & Heinecke, J. W. Dissociation between tissue iron concentrations and transferrin saturation among inbred mouse strains. J. Lab. Clin. Med. 126, 128–136 (1995).
pubmed: 7636385
Martin, D. et al. Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload. J. Cachexia Sarcopenia Muscle 13, 1250–1261. https://doi.org/10.1002/jcsm.12897 (2022).
doi: 10.1002/jcsm.12897
pubmed: 35118832
pmcid: 8978014
Li, L. B. et al. Iron exposure and the cellular mechanisms linked to neuron degeneration in adult mice. Cells https://doi.org/10.3390/cells8020198 (2019).
doi: 10.3390/cells8020198
pubmed: 31892265
pmcid: 7017176
Musumeci, M. et al. Iron excretion in iron dextran-overloaded mice. Blood Transfus 12, 485–490. https://doi.org/10.2450/2014.0288-13 (2014).
doi: 10.2450/2014.0288-13
pubmed: 24960657
pmcid: 4212028
Musumeci, M. et al. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice. Blood Transfus 11, 88–93. https://doi.org/10.2450/2012.0176-11 (2013).
doi: 10.2450/2012.0176-11
pubmed: 22790263
pmcid: 3557493