Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin

Balogh, Enikő; Tolnai, Emese; Nagy, Béla; Balla, György; Balla, József; Jeney, Viktória

doi:10.1016/j.bbadis.2016.06.003

Cited by 117 publications

(99 citation statements)

References 51 publications

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“…Other in vitro studies on human osteoblasts suggested that the ferroxidase activity of ferritin that inhibits the mineralization and downregulates the alkaline phosphate expression and activity [39], both, could be explanations for low cortical BMD. Iron selectively inhibits differentiation of multipotent mesenchymal stem cells to osteoblasts [40]. This is in line with studies on HHC patients, a negative impact of hepatic iron concentrations on BMD, [10] and an association of osteoporosis with the severity of iron overload at diagnosis (reflected by serum ferritin levels or iron removed to reach depletion), but transferrin saturation was not determined [11,20].…”

Section: Pathophysiological Explanatory Approachessupporting

confidence: 78%

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

et al. 2020

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Hereditary hemochromatosis (HHC) is characterized by excessive intestinal iron absorption resulting in a pathological increase of iron levels. Parenchyma damage may be a consequence of iron deposition in affected organs (e.g., liver, pancreas, gonads) as well as bones and joints, leading to osteoporosis with increased fracture risk and arthropathy. Up to date, it is not known whether HHC can also be considered as a risk factor for osteonecrosis. Likewise, the underlying skeletal changes are unknown regarding, e.g., microstructural properties of bone. We aimed to study the spectrum of skeletal complications in HHC and the possible underlying microarchitectural changes. Therefore, we retrospectively analyzed all patients with HHC (n = 10) presenting in our outpatient clinic for bone diseases. In addition to dual-energy X-ray absorptiometry (DXA), highresolution peripheral quantitative computed tomography (HR-pQCT) was performed and bone turnover markers, 25-OH-D3, ferritin and transferrin saturation were measured. Cortical volumetric bone mineral density (Ct.BMD) and cortical thickness (Ct.Th) were reduced, whereas trabecular microstructure (Tb.Th) and volumetric bone mineral density (Tb.BMD) were preserved compared to age-and gender-adjusted reference values from the literature. Interestingly, the occurrence of bone complications was age dependent; while younger patients presented with osteonecroses or transient bone marrow edema, patients older than 65 years presented with fractures. Our study provides first insights into altered bone microarchitecture in HHC and sheds new light on the occurrence of osteonecrosis. If available, HR-pQCT is a useful complement to fracture risk assessment and to determine microstructural deterioration and volumetric bone mineralization deficits.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Pathophysiological Explanatory Approachessupporting

confidence: 78%

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

et al. 2020

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“…In vivo experiments in mice were able to reproduce these findings. The inhibitory effect of iron, however, was specific for osteogenic lineage differentiation, whereas no impact on chondrogenesis and adipogenesis was noted [163].…”

Section: Iron (Fe 2+ )mentioning

confidence: 92%

Applications of Metals for Bone Regeneration

Glenske¹,

Donkiewicz²,

Köwitsch³

et al. 2018

Preprint

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The regeneration of bone tissue is a main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, while it should be resorbed even in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated and it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also on osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between the formation of new bone tissue and material degradation has not been found until now. The addition of different substances such as collagen or growth factors and also of different cell types have already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are differently used as basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designated for bone regeneration with the aim to give an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

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“…Iron overload in mice results in increased bone resorption and oxidative stress, leading to changes in bone microarchitecture and bone loss. Iron can directly inhibit osteogenic commitment and bone marrow stromal cell differentiation [ 92 ]; however, the underlying mechanism remains unknown.…”

Section: Molecular Mechanism Of Bone Remodeling and Osteoporosismentioning

confidence: 99%

Molecular Mechanisms and Emerging Therapeutics for Osteoporosis

Noh

Yang

Jung

2020

IJMS

167

121

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Osteoporosis is the most common chronic metabolic bone disease. It has been estimated that more than 10 million people in the United States and 200 million men and women worldwide have osteoporosis. Given that the aging population is rapidly increasing in many countries, osteoporosis could become a global challenge with an impact on the quality of life of the affected individuals. Osteoporosis can be defined as a condition characterized by low bone density and increased risk of fractures due to the deterioration of the bone architecture. Thus, the major goal of treatment is to reduce the risk for fractures. There are several treatment options, mostly medications that can control disease progression in risk groups, such as postmenopausal women and elderly men. Recent studies on the basic molecular mechanisms and clinical implications of osteoporosis have identified novel therapeutic targets. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for osteoporosis management in the future. Here, we review the etiology of osteoporosis and the molecular mechanism of bone remodeling, present current pharmacological options, and discuss emerging therapies targeting novel mechanisms, investigational treatments, and new promising therapeutic approaches.

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Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin

Cited by 117 publications

References 51 publications

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications

Applications of Metals for Bone Regeneration

Molecular Mechanisms and Emerging Therapeutics for Osteoporosis

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