Open AccessDifferential 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
Author(s) -
Kornkamon Lertsuwan,
Ketsaraporn Nammultriputtar,
Supanan Nanthawuttiphan,
Natnicha Tannop,
Jarinthorn Teerapornpuntakit,
Jirawan Thongbunchoo,
Narattaphol Charoenphandhu
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0234009
Subject(s) - deferiprone , osteoblast , chemistry , calcium , extracellular , deferoxamine , viability assay , microbiology and biotechnology , endocrinology , biochemistry , medicine , apoptosis , biology , organic chemistry , in vitro
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 Fe 3+ and Fe 2+ on osteoblast differentiation and mineralization were studied in UMR-106 osteoblast cells by using ferric ammonium citrate and ferrous ammonium sulfate as Fe 3+ and Fe 2+ donors, respectively. Effects of 1,25 dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and iron chelator deferiprone on iron uptake ability of osteoblasts were examined, and the potential protective ability of 1,25(OH) 2 D 3 , deferiprone and extracellular calcium treatment in osteoblast cell survival under iron overload was also elucidated. The differential effects of Fe 3+ and Fe 2+ 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 Fe 3+ than Fe 2+ . 1,25(OH) 2 D 3 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 Fe 3+ . In conclusions, Fe 3+ and Fe 2+ differentially compromised the osteoblast functions and viability, which can be alleviated by an increase in extracellular ionized calcium, but not 1,25(OH) 2 D 3 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.