Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Zhang, Peng; Wang, Sheng; Wang, Liang; Shan, Bing; Zhang, Hui; Yang, Fan; Zhou, Zhi; Xiao, Wang; Yuan, Ye; Xu, You Sheng

doi:10.1530/jme-17-0301

Cited by 28 publications

(11 citation statements)

References 35 publications

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“…In contrast, supplementation with hepcidin and reduction in ferritin protected against femur bone loss in these mice [ 34 ]. In this study, the levels of ferritin and bone iron in mice were reduced after hepcidin overexpression, which was consistent with the results of previous studies [ 35 , 36 ]. Overexpression of hepcidin significantly protected bone mass and BMD caused by OVX.…”

Section: Discussionsupporting

confidence: 93%

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis

Zhang

Wang

Shen

et al. 2021

Aging

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As a necessary trace element, iron is involved in many physiological processes. Clinical and basic studies have found that disturbances in iron metabolism, especially iron overload, might lead to bone loss and even be involved in postmenopausal osteoporosis. Hepcidin is a key regulator of iron homeostasis. However, the exact role of hepcidin in bone metabolism and the underlying mechanism remain unknown. In this study, we found that in postmenopausal osteoporosis cohort, the concentration of hepcidin in the serum was significantly reduced and positively correlated with bone mineral density. Ovariectomized (OVX) mice were then used to construct an osteoporosis model. Hepcidin overexpression in these mice significantly improved bone mass and rescued the phenotype of bone loss. Additionally, overexpression of hepcidin in OVX mice greatly reduced the number and differentiation of osteoclasts in vivo and in vitro . This study found that overexpression of hepcidin significantly inhibited ROS production, mitochondrial biogenesis, and PGC-1β expression. These data showed that hepcidin protected osteoporosis by reducing iron levels in bone tissue, and in conjunction with PGC-1β, reduced ROS production and the number of mitochondria, thus inhibiting osteoclast differentiation and bone absorption. Hepcidin could provide new targets for the clinical treatment of postmenopausal osteoporosis.

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Section: Discussionsupporting

confidence: 93%

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis

Zhang

Wang

Shen

et al. 2021

Aging

Self Cite

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“…Iron accumulation is a risk factor for osteoporosis, and hepcidin is expected to be a useful therapeutic target [23][24][25] . In one study, hepcidin knockout mice had a higher serum ferritin level and higher iron in the liver and femur than controls and showed low bone mass and changes in bone microarchitecture 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Hepcidin knockout mice also showed a marked reduction in bone load-bearing capacity with enhanced bone resorption 23 . A mouse model with overexpression of hepcidin showed higher levels of serum hepcidin and lower levels of serum ferritin, and bone loss and changes in markers of bone metabolism after ovariectomy were ameliorated 24 . In humans, genetic hemochromatosis and thalassemia cause iron overload, and osteoporosis is a major complication 11,12 .…”

Section: Discussionmentioning

confidence: 99%

Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthritis

Sato

Takai

Kazama

et al. 2020

Sci Rep

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Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

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“…MSCs can secrete the iron hormone hepcidin (Esfandiyari et al, 2019). Since excess iron is a risk factor for osteoporosis (Weinberg, 2006), it is possible that the MSC‐secreted hepcidin reduce local tissue iron levels and thereby act as an endogenous protector against the development of osteoporosis (Zhang et al, 2018). Hepcidin may also execute its anti‐bone‐loss function by modulating BM‐MSC differentiation.…”

Section: Iron and Iron‐related Endogenous Effectors Of Mscsmentioning

confidence: 99%

Role of iron and iron‐related proteins in mesenchymal stem cells: Cellular and clinical aspects

Mehta

2021

Journal Cellular Physiology

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Mesenchymal stem cells (MSCs) are located in various tissues where these cells show niche‐dependent multilineage differentiation and secrete immunomodulatory molecules to support numerous physiological processes. Due to their regenerative and reparative properties, MSCs are extremely valuable for cell‐based therapy in tackling several pathological conditions including COVID‐19. Iron is essential for MSC processes but iron‐loading, which is common in several chronic conditions, hinders normal MSC functionality. This not only aggravates disease pathology but can also affect allogeneic and autologous MSC therapy. Thus, understanding MSCs from an iron perspective is of clinical significance. Accordingly, this review highlights the roles of iron and iron‐related proteins in MSC physiology. It describes the contribution of iron and endogenous iron‐related effectors like hepcidin, ferroportin, transferrin receptor, lactoferrin, lipocalin‐2, bone morphogenetic proteins and hypoxia inducible factors in MSC biology. It summarises the excess‐iron‐induced alterations in MSC components, processes and discusses signalling pathways involving ROS, PI3K/AKT, MAPK, p53, AMPK/MFF/DRP1 and Wnt. Additionally, it evaluates the endogenous and exogenous saviours of MSCs against iron‐toxicity. Lastly, it elaborates on the involvement of MSCs in the pathology of clinical conditions of iron‐excess, namely, hereditary hemochromatosis, diabetes, β‐thalassaemia and myelodysplastic syndromes. This unique review integrates the distinct fields of iron regulation and MSC physiology. Through an iron‐perspective, it describes both mechanistic and clinical aspects of MSCs and proposes an iron‐linked MSC‐contribution to physiology, pathology and therapeutics. It advances the understanding of MSC biology and may aid in identifying signalling pathways, molecular targets and compounds for formulating adjunctive iron‐based therapies for excess‐iron conditions, and thereby inform regenerative medicine.

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Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels

Cited by 28 publications

References 35 publications

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis

Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthritis

Role of iron and iron‐related proteins in mesenchymal stem cells: Cellular and clinical aspects

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