Differential effects of Fe2+ and Fe3+ on osteoblasts and the effects of 1,25(OH)2D3, deferiprone and extracellular calcium on osteoblast viability under iron-overloaded conditions

Autor: Jirawan Thongbunchoo, Ketsaraporn Nammultriputtar, Jarinthorn Teerapornpuntakit, Kornkamon Lertsuwan, Narattaphol Charoenphandhu, Natnicha Tannop, Supanan Nanthawuttiphan
Rok vydání: 2020
Předmět:
0301 basic medicine
Biochemistry
chemistry.chemical_compound
Oxidative Damage
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Deferiprone
Cell Cycle and Cell Division
Connective Tissue Diseases
Connective Tissue Cells
Multidisciplinary
Cell Death
Osteoblast
Cell Differentiation
Osteoblast Differentiation
Cell biology
medicine.anatomical_structure
Connective Tissue
Cell Processes
030220 oncology & carcinogenesis
Alkaline phosphatase
Medicine
Cellular Types
Anatomy
Intracellular
medicine.drug
Research Article
inorganic chemicals
Iron Overload
Cell Survival
Science
Iron
chemistry.chemical_element
Calcium
Cell Line
03 medical and health sciences
Calcification
Physiologic
Calcitriol
Rheumatology
Extracellular
medicine
Animals
Calcium metabolism
Osteoblasts
Biology and Life Sciences
Proteins
Cell Cycle Checkpoints
Cell Biology
Rats
Gastrointestinal Tract
030104 developmental biology
Biological Tissue
chemistry
Ferric
Osteoporosis
Extracellular Space
Reactive Oxygen Species
Digestive System
Collagens
Biomarkers
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 5, p e0234009 (2020)
ISSN: 1932-6203
Popis: One of the potential contributing factors for iron overload-induced osteoporosis is the iron toxicity on bone forming cells, osteoblasts. In this study, the comparative effects of Fe3+ and Fe2+ on osteoblast differentiation and mineralization were studied in UMR-106 osteoblast cells by using ferric ammonium citrate and ferrous ammonium sulfate as Fe3+ and Fe2+ donors, respectively. Effects of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] and iron chelator deferiprone on iron uptake ability of osteoblasts were examined, and the potential protective ability of 1,25(OH)2D3, deferiprone and extracellular calcium treatment in osteoblast cell survival under iron overload was also elucidated. The differential effects of Fe3+ and Fe2+ on reactive oxygen species (ROS) production in osteoblasts were also compared. Our results showed that both iron species suppressed alkaline phosphatase gene expression and mineralization with the stronger effects from Fe3+ than Fe2+. 1,25(OH)2D3 significantly increased the intracellular iron but minimally affected osteoblast cell survival under iron overload. Deferiprone markedly decreased intracellular iron in osteoblasts, but it could not recover iron-induced osteoblast cell death. Interestingly, extracellular calcium was able to rescue osteoblasts from iron-induced osteoblast cell death. Additionally, both iron species could induce ROS production and G0/G1 cell cycle arrest in osteoblasts with the stronger effects from Fe3+. In conclusions, Fe3+ and Fe2+ differentially compromised the osteoblast functions and viability, which can be alleviated by an increase in extracellular ionized calcium, but not 1,25(OH)2D3 or iron chelator deferiprone. This study has provided the invaluable information for therapeutic design targeting specific iron specie(s) in iron overload-induced osteoporosis. Moreover, an increase in extracellular calcium could be beneficial for this group of patients.
Databáze: OpenAIRE
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