ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2012
Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells.
Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis.Journal of bone and mineral metabolism · 2016Trial
- Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance.PloS one · 2013Trial
- Targeting ferroptosis in osteoporosis: mechanisms and natural products therapies.Frontiers in pharmacology · 2026Review
- The influence of iron on bone metabolism disorders.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Role of Iron Accumulation in Osteoporosis and the Underlying Mechanisms.Current medical science · 2023Article
- Dietary iron intake and its impact on osteopenia/osteoporosis.BMC endocrine disorders · 2023Article
- Iron accumulation and its impact on osteoporotic fractures in postmenopausal women.Journal of Zhejiang University. Science. B · 2023Review
- Iron, Zinc, Copper, Cadmium, Mercury, and Bone Tissue.International journal of environmental research and public health · 2023Review
- Exploring the Association between Glutathione Metabolism and Ferroptosis in Osteoblasts with Disuse Osteoporosis and the Key Genes Connecting them.Computational and mathematical methods in medicine · 2022Article
- Review
- Iron Overload Induces Apoptosis and Cytoprotective Autophagy Regulated by ROS Generation in Mc3t3-E1 Cells.Biological trace element research · 2021Article
- Iron accumulation deteriorated bone loss in estrogen-deficient rats.Journal of orthopaedic surgery and research · 2021Article
- Hepcidin deficiency causes bone loss through interfering with the canonical Wnt/β-catenin pathway via Forkhead box O3a.Journal of orthopaedic translation · 2020Article
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- Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study.Bone & joint research · 2019Article
- Influence of Iron on Bone Homeostasis.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Iron excess upregulates SPNS2 mRNA levels but reduces sphingosine-1-phosphate export in human osteoblastic MG-63 cells.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2018Article
- δ-Tocotrienol feeding modulates gene expression of EIF2, mTOR, protein ubiquitination through multiple-signaling pathways in chronic hepatitis C patients.Lipids in health and disease · 2018Article
- Clinical Impact and Cellular Mechanisms of Iron Overload-Associated Bone Loss.Frontiers in pharmacology · 2017Review
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledIn order to understand mechanisms involved in osteoporosis observed during iron overload diseases, we analyzed the impact of iron on a human osteoblast-like cell line. Iron exposure decreases osteoblast phenotype. HHIPL-2 is an iron-modulated gene which could contribute to these alterations. Our results suggest osteoblast impairment in iron-related osteoporosis.
introductionIron overload may cause osteoporosis. An iron-related decrease in osteoblast activity has been suggested.
methodsWe investigated the effect of iron exposure on human osteoblast cells (MG-63) by analyzing the impact of ferric ammonium citrate (FAC) and iron citrate (FeCi) on the expression of genes involved in iron metabolism or associated with osteoblast phenotype. A transcriptomic analysis was performed to identify iron-modulated genes.
resultsFAC and FeCi exposure modulated cellular iron status with a decrease in TFRC mRNA level and an increase in intracellular ferritin level. FAC increased ROS level and caspase 3 activity. Ferroportin, HFE and TFR2 mRNAs were expressed in MG-63 cells under basal conditions. The level of ferroportin mRNA was increased by iron, whereas HFE mRNA level was decreased. The level of mRNA alpha 1 collagen type I chain, osteocalcin and the transcriptional factor RUNX2 were decreased by iron. Transcriptomic analysis revealed that the mRNA level of HedgeHog Interacting Protein Like-2 (HHIPL-2) gene, encoding an inhibitor of the hedgehog signaling pathway, was decreased in the presence of FAC. Specific inhibition of HHIPL-2 expression decreased osteoblast marker mRNA levels. Purmorphamine, hedgehog pathway activator, increased the mRNA level of GLI1, a target gene for the hedgehog pathway, and decreased osteoblast marker levels. GLI1 mRNA level was increased under iron exposure.
conclusionWe showed that in human MG-63 cells, iron exposure impacts iron metabolism and osteoblast gene expression. HHIPL-2 gene expression modulation may contribute to these alterations. Our results support a role of osteoblast impairment in iron-related osteoporosis.
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