Ferrous and ferric differentially deteriorate proliferation and differentiation of osteoblast-like UMR-106 cells
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The association between iron overload and osteoporosis has been found in many diseases, such as hemochromatosis, β-thalassemia and sickle cell anemia with multiple blood transfusion. One of the contributing factors is iron toxicity to osteoblasts. Some studies showed the negative effects of iron on osteoblasts; however, the effects of two biological available iron species, i.e., ferric and ferrous, on osteoblasts are elusive. Since most intracellular ionized iron is ferric, osteoblasts was hypothesized to be more responsive to ferric iron. Herein, ferric ammonium citrate (FAC) and ferrous ammonium sulfate (FAS) were used as ferric and ferrous donors. Our results showed that both iron species suppressed cell survival and proliferation. Both also induced osteoblast cell death consistent with the higher levels of cleaved caspase 3 and caspase 7 in osteoblasts, indicating that iron induced osteoblast apoptosis. Iron treatments led to the elevated intracellular iron in osteoblasts as determined by atomic absorption spectrophotometry, thereby leading to a decreased expression of genes for cellular iron import and increased expression of genes for cellular iron export. Effects of FAC and FAS on osteoblast differentiation were determined by the activity of alkaline phosphatase (ALP). The lower ALP activity from osteoblast with iron exposure was found. In addition, ferric and ferrous differentially induced osteoblastic and osteoblast-derived osteoclastogenic gene expression alterations in osteoblast. Even though both iron species had similar effects on osteoblast cell survival and differentiation, the overall effects were markedly stronger in FAC-treated groups, suggesting that osteoblasts were more sensitive to ferric than ferrous.
KeywordsAlkaline phosphatase Ferric Ferrous Iron overload Osteoblast
This work was supported by Grants from the Thailand Research Fund (TRF) through the TRF Senior Research Scholar Grant (RTA6080007 to N. Charoenphandhu), TRF International Research Network Program (IRN60W0001 to K. Wongdee and N. Charoenphandhu), Research Grant for New Scholar from TRF, Office of the Higher Education Commission and Mahidol University (MRG6180268 to K. Lertsuwan), RD&E funding (SCH-NR2016-141) from National Science and Technology Development Agency, Thailand, and the CIF grant, Faculty of Science, Mahidol University.
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Conflict of interest
The authors declare that there is no conflict of interest.
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