Iron Accumulation Leads to Bone Loss by Inducing Mesenchymal Stem Cell Apoptosis Through the Activation of Caspase3

Yuan, Ye; Xu, Fei; Cao, Yan; Xu, Li; Yu, Chen; Yang, Fan; Zhang, Peng; Wang, Liang; Shen, Genhai; Wang, Jianrong; Xu, Youjia

doi:10.1007/s12011-018-1388-9

Cited by 34 publications

(38 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it has been reported that the low expression of miR‐758‐3p in the serum of osteoporosis patients affects the progress of osteoporosis 17 . Multiple studies have highlighted that IA could cause bone loss or dysfunction through the activation of caspase 3‐mediated cell apoptosis 18,31 . In this study, our results showed that the expression of BAX was up‐regulated while that of BCL2 was down‐regulated upon IA, which also demonstrated the IA‐mediated cell apoptosis.…”

Section: Discussionsupporting

confidence: 57%

“…Sufficient water and food were given during the experiment. These mice were randomly divided into groups ( n = 5), including a diet supplemented with 25 g/kg of carbonyl iron for 14 days and standard chow diet (180 mg of iron/kg) served as controls 18 . Adenoviruses of shXIST or miR‐758‐3p mimics were injected through tail vein.…”

Section: Methodsmentioning

confidence: 99%

“…Multiple miRNAs have been revealed to be dysregulated in osteoporotic patients and the potential role of miRNAs as biomarkers for diagnose is considered 1,16 In the serum of osteoporosis patients, the level of miR‐758‐3p was down‐regulated, indicating its role in osteoporosis development 17 . IA can activate caspase 3 by promoting bone marrow mesenchymal stem cell apoptosis, which in turn leads to osteoporosis 18 . However, the interaction mechanism of miR‐758‐3p and caspase 3 in IA‐induced osteoporosis has not been reported.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Iron accumulation regulates osteoblast apoptosis through lncRNAXIST/miR‐758‐3p/caspase 3 axis leading to osteoporosis

Wang

Chen

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

Postmenopausal osteoporosis (PMOP) is mainly caused by multiple factors. Recent studies have suggested that iron accumulation (IA) was closely related to PMOP. However, the detailed molecular mechanisms have not been well demonstrated. We constructed the IA mouse model by intraperitoneal injections of ferric ammonium citrate (FAC) and cell model by culturing with the medium containing FAC. Osteoporosis was confirmed in mouse bone tissues using H&E staining, and the level of serum ferritin, alkaline phosphatase (ALP), procollagen-1 N-terminal peptide (P1NP), and osteocalcin in mice was examined by ELISA. The expressions of XIST and miR-758-3p were detected by qRT-PCR. Cell proliferation and apoptosis were measured by CCK-8, TUNEL, and flow cytometry. The expression levels of apoptotic-related proteins were evaluated by western blot. Dual luciferase reporter assay was used to examine the molecular interaction. The expressions of ALP, P1NP, and osteocalcin, and the H&E staining of bone tissues in mice were analyzed to confirm the biological function of XIST and miR-758-3p in vivo. XIST was up-regulated while miR-758-3p was down-regulated in IA mouse and cell models. XIST knockdown significantly reduced FAC-induced osteoblast apoptosis, which was mimicked by transfection with miR-758-3p mimics. XIST acted as a sponge of miR-758-3p, which targeted caspase 3. IA led to the high expression of XIST and promoted osteoblast apoptosis through miR-758-3p/caspase 3. Transfection with shXIST or miR-758-3p mimics alleviated IA-induced mouse osteoporosis. IA regulated osteoblast apoptosis through XIST/miR-758-3p/caspase 3 axis, which might provide alternative targets for the treatment of osteoporosis.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Iron accumulation regulates osteoblast apoptosis through lncRNAXIST/miR‐758‐3p/caspase 3 axis leading to osteoporosis

Wang

Chen

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…Iron accumulation in menopausal females often increases risk in osteoporosis, largely attributed to less loss of blood (Kim et al, ; Rachner et al, ; Tsay et al, ; Xiao et al, ; Yuan et al, ). To determine whether osteoporosis from iron overload is also associated with hematopoietic dysfunction at the HSPC level, we generated iron accumulation‐induced osteoporotic mice (Tsay et al, ).…”

Section: Resultsmentioning

confidence: 99%

Deterioration of hematopoietic autophagy is linked to osteoporosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy-defective mice.Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy-defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis. SPSS 25.0. Experimental data were presented as means ± standard deviations (SDs), which was evaluated using Student's t tests.University, for their help in preparing human bone samples and creating mouse osteoporotic model, and Jin Qi from the Shanghai

show abstract

“…120 Iron can also induce death of neurons through apoptosis, a form of cell death triggered by the release of cytochrome c from mitochondria and subsequent activation of caspase-3 or by the activation of caspase-8 through binding of ligands, such as TNF or FasL, to their receptors at the plasma membrane. [121][122][123] Although most effort has been placed on the effects of iron on neurons, it is now well-accepted that dysfunction of glial cells makes key contributions to the pathogenesis of neurodegenerative disorders. [124][125][126][127] Iron is required for the proper development of oligodendrocytes and a high amount of ferritin-bound iron is necessary for synthesis of myelin and fatty acid synthesis.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

show abstract

Iron Accumulation Leads to Bone Loss by Inducing Mesenchymal Stem Cell Apoptosis Through the Activation of Caspase3

Cited by 34 publications

References 44 publications

Iron accumulation regulates osteoblast apoptosis through lncRNAXIST/miR‐758‐3p/caspase 3 axis leading to osteoporosis

Iron accumulation regulates osteoblast apoptosis through lncRNAXIST/miR‐758‐3p/caspase 3 axis leading to osteoporosis

Deterioration of hematopoietic autophagy is linked to osteoporosis

Overdosing on iron: Elevated iron and degenerative brain disorders

Contact Info

Product

Resources

About