Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis
| Autor: | Agnès Ostertag, M. Leonor Cancela, I. Jorge Pinto, Antonio Camacho, Ea Hang Korng, Graça Porto, Martine Cohen-Solal, Márcio Simão |
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| Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Bone density Organogenesis Osteoporosis lcsh:Medicine Pathology and Laboratory Medicine Hemochromatosis / pathology Osteoporosis / genetics Biochemistry Osteogenesis / genetics Bone remodeling Mice Animal Cells Medicine and Health Sciences Femur Age of Onset lcsh:Science Musculoskeletal System Immune Response Connective Tissue Cells chemistry.chemical_classification Mice Knockout Osteogenesis / drug effects Multidisciplinary biology Animal Models Iron Overload / pathology Hemochromatosis Protein / genetics Osteoporosis / diet therapy 3. Good health Osteoporosis / complications Chemistry Phenotype Experimental Organism Systems Hemochromatosis / genetics Liver Connective Tissue Hereditary hemochromatosis Physical Sciences Cellular Types Anatomy Antigens CD / genetics Research Article Chemical Elements medicine.medical_specialty Iron Bone and Mineral Metabolism Immunology Mouse Models Research and Analysis Methods Bone resorption 03 medical and health sciences Hemochromatosis / diet therapy Model Organisms Signs and Symptoms Diagnostic Medicine Internal medicine medicine Animals Humans Ferritins / genetics Skeleton Hemochromatosis Nutrition Inflammation Bone Development Osteoblasts Osteoblasts / drug effects business.industry lcsh:R Biology and Life Sciences Cell Biology Osteoporosis / pathology medicine.disease Hemochromatosis / complications Iron Overload / complications Diet Ferritin Disease Models Animal Biological Tissue Metabolism 030104 developmental biology Endocrinology chemistry Transferrin Iron Overload / genetics Iron Overload / diet therapy Iron Dietary / administration & dosage Animal Studies biology.protein Receptors Transferrin / genetics lcsh:Q business Organism Development Developmental Biology |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação PLoS ONE, Vol 13, Iss 11, p e0207441 (2018) PLoS ONE |
| Popis: | Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions. his research was partially supported by National Funds through Foundation for Science and Technology (FCT), under the project “CCMAR/Multi/04326/2013” and Norte-01-0145-FEDER-000012 –“Structured program on bioengineered therapies for infectious diseases and tissue regeneration”. M. Simão was supported by a PhD fellowship from the Portuguese Foundation for Science and Technology (FCT) with the reference SFRH/BD/77056/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. info:eu-repo/semantics/publishedVersion |
| Databáze: | OpenAIRE |
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