scholarly journals Effects of Erythropoietin in White Adipose Tissue and Bone Microenvironment

2020 ◽  
Vol 8 ◽  
Author(s):  
Sukanya Suresh ◽  
Jeeyoung Lee ◽  
Constance Tom Noguchi
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Fat Mass ◽  
Bone Development ◽  
Erythropoietin Receptor ◽  
Receptor Expression ◽  
High Dose ◽  
Obese Mice ◽  
Erythroid Progenitor ◽  
Increase Fracture Risk

Erythropoietin (EPO) is expressed primarily in fetal liver and adult kidney to stimulate red blood cell production. Erythropoietin receptor expression is not restricted to erythroid progenitor cells, and non-erythroid EPO activity includes immune response and bone remodeling. In bone fracture models, EPO administration promotes bone formation and accelerates bone healing. In contrast, in healthy adult mice, exogenous EPO-stimulated erythropoiesis has been concomitant with bone loss, particularly at high EPO, that may be accompanied by increased osteoclast activation. Other EPO-associated responses include reduced inflammation and loss of fat mass with high-fat diet feeding, especially in male mice. While EPO exhibited a sex-dimorphic response in regulation of fat mass and inflammation in obese mice, EPO-stimulated erythropoiesis as well as EPO-associated bone loss was comparable in males and females. EPO administration in young mice and in obese mice resulted in bone loss without increasing osteoclasts, suggesting an osteoclast-independent mechanism, while loss of endogenous EPO decreased bone development and maintenance. Ossicle formation of bone marrow stromal cell transplants showed that EPO directly regulates the balance between osteogenesis and adipogenesis. Therefore, during development, endogenous EPO contributes to normal bone development and in maintaining the balance between osteogenesis and adipogenesis in bone marrow stromal cells, while EPO treatment in mice increased erythropoiesis, promoted bone loss, decreased bone marrow adipogenesis, and increased osteoclast activity. These observations in mouse models suggest that the most prevalent use of EPO to treat anemia associated with chronic kidney disease may compromise bone health and increase fracture risk, especially at a high dose.

scholarly journals Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.

1995 ◽  
Vol 15 (6) ◽  
pp. 3147-3153 ◽  
Author(s):  
G A Blobel ◽  
C A Sieff ◽  
S H Orkin
Keyword(s):  
Bone Marrow ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Progenitor Cells ◽  
Erythroid Cell ◽  
High Dose ◽  
Dependent Manner ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation.

scholarly journals Erythropoietin in Brain Development and Beyond

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Mawadda Alnaeeli ◽  
Li Wang ◽  
Barbora Piknova ◽  
Heather Rogers ◽  
Xiaoxia Li ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Cell Types ◽  
Erythropoietin Receptor ◽  
Adult Brain ◽  
Receptor Expression ◽  
Neural Cells ◽  
Erythroid Progenitor ◽  
Cell Production ◽  
Oxygen Carrying Capacity

Erythropoietin is known as the requisite cytokine for red blood cell production. Its receptor, expressed at a high level on erythroid progenitor/precursor cells, is also found on endothelial, neural, and other cell types. Erythropoietin and erythropoietin receptor expression in the developing and adult brain suggest their possible involvement in neurodevelopment and neuroprotection. During ischemic stress, erythropoietin, which is hypoxia inducible, can contribute to brain homeostasis by increasing red blood cell production to increase the blood oxygen carrying capacity, stimulate nitric oxide production to modulate blood flow and contribute to the neurovascular response, or act directly on neural cells to provide neuroprotection as demonstrated in culture and animal models. Clinical studies of erythropoietin treatment in stroke and other diseases provide insight on safety and potential adverse effects and underscore the potential pleiotropic activity of erythropoietin. Herein, we summarize the roles of EPO and its receptor in the developing and adult brain during health and disease, providing first a brief overview of the well-established EPO biology and signaling, its hypoxic regulation, and role in erythropoiesis.

scholarly journals Increased erythropoietin-receptor expression on CD34-positive bone marrow cells from patients with chronic myeloid leukemia

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 642-649 ◽  
Author(s):  
AW Wognum ◽  
G Krystal ◽  
CJ Eaves ◽  
AC Eaves ◽  
PM Lansdorp
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Erythropoietin Receptor ◽  
Receptor Expression ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Normal Individuals ◽  
Marrow Cells

Abstract Erythropoietin-receptor (EpR) expression on bone marrow cells from normal individuals and from patients with chronic myeloid leukemia (CML) was examined by multiparameter flow cytometry after stepwise amplified immunostaining with biotin-labeled Ep, streptavidin- conjugated R-phycoerythrin, and biotinylated monoclonal anti-R- phycoerythrin. This approach allowed the detection of EpR-positive cells in all bone marrow samples studied. Most of the EpR-positive cells in normal bone marrow were found to be CD45-dull, CD34-negative, transferrin-receptor-positive and glycophorin-A-intermediate to - positive. This phenotype is characteristic of relatively mature erythroid precursors, ie, colony-forming units-erythroid and erythroblasts recognizable by classic staining procedures. Approximately 5% of normal EpR-positive cells displayed an intermediate expression of CD45, suggesting that these represented precursors of the CD45-dull EpR-positive cells. Some EpR-positive cells in chronic myeloid leukemia (CML) bone marrow had a phenotype similar to the major EpR-positive phenotype in normal bone marrow, ie, CD34-negative and CD45-dull. However, there was a disproportionate increase in the relative number of EpR-positive/CD45-intermediate cells in CML bone marrow. Even more striking differences between normal individuals and CML patients were observed when EpR-expression on CD34-positive marrow cells was analyzed. Very few EpR-positive cells were found in the CD34- positive fraction of normal bone marrow, whereas a significant fraction of the CD34-positive marrow cells from five of five CML patients expressed readily detectable EpR. These findings suggest that control of EpR expression is perturbed in the neoplastic clone of cells present in patients with CML. This may be related to the inadequate output of mature red blood cells typical of CML patients and may also be part of a more generalized perturbation in expression and/or functional integrity of other growth factor receptors on CML cells.

A Novel Way to Induce Erythroid Progenitor Self Renewal: Cooperation of c-Kit with the Erythropoietin Receptor

1999 ◽  
Vol 380 (2) ◽  
Author(s):  
O. Wessely ◽  
A. Bauer ◽  
C. Tran Quang ◽  
E.-M. Deiner ◽  
M. von Lindern ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Erythropoietin Receptor ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Self Renewal ◽  
Transforming Growth Factor Α ◽  
Factor Α

AbstractRed blood cells are of vital importance for oxygen transport in vertebrates. Thus, their formation during development and homeostasis requires tight control of both progenitor proliferation and terminal red cell differentiation. Self renewal (i.e. long-term proliferation without differentiation) of committed erythroid progenitors has recently been shown to contribute to this regulation. Avian erythroid progenitors expressing the EGF receptor/c-ErbB (SCF/TGFα progenitors) can be induced to long-term proliferation by the c-ErbB ligand transforming growth factor α and the steroids estradiol and dexamethasone. These progenitors have not yet been described in mammals and their factor requirements are untypical for adult erythroid progenitors. Here we describe a second, distinct type of erythroid progenitor (EpoR progenitors) which can be established from freshly isolated bone marrow and is induced to self renew by ligands relevant for erythropoiesis, i.e. erythropoietin, stem cell factor, the ligand for c-Kit and the glucocorticoid receptor ligand dexamethasone. Limiting dilution cloning indicates that these EpoR progenitors are derived from normal BFU-E/CFU-E. For a detailed study, mEpoR progenitors were generated by retroviral expression of the murine Epo receptor in bone marrow erythroblasts. These progenitors carry out the normal erythroid differentiation program in recombinant differentiation factors only. We show that mEpoR progenitors are more mature than SCF/TGFα progenitors and also do no longer respond to transforming growth factor α and estradiol. In contrast they are now highly sensitive to low levels of thyroid hormone, facilitating their terminal maturation into erythrocytes.

scholarly journals The Anemic Friend Virus gp55 Envelope Protein Induces Erythroid Differentiation in Fetal Liver Colony-Forming Units-Erythroid

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1163-1172 ◽  
Author(s):  
Stefan N. Constantinescu ◽  
Hong Wu ◽  
Xuedong Liu ◽  
Wendy Beyer ◽  
Amy Fallon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Fetal Liver ◽  
Erythroid Differentiation ◽  
Liver Cells ◽  
Erythropoietin Receptor ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Fetal Liver Cells

Abstract The gp55 envelope proteins of the spleen focus-forming virus initiate erythroleukemia in adult mice. Because the gp55 from the polycythemic strain (gp55-P), but not from the anemic strain (gp55-A), activates the erythropoietin receptor (EpoR) for proliferation of hematopoietic cell lines, the mechanism by which gp55-A initiates erythroleukemia has remained a mystery. We show here that gp55-A activates the EpoR in fetal liver cells. In contrast to previous studies using bone marrow cells from phenylhydrazine-treated, anemic mice, we find that both gp55-A and gp55-P induce erythroid differentiation from colony-forming unit-erythroid (CFU-E) progenitors in fetal liver cells. The effects on CFU-Es of both gp55-A and -P are mediated by the EpoR, because no colonies are seen upon expression of either gp55 in EpoR−/− fetal liver cells. However, only gp55-P induces erythroid bursts from burst-forming unit-erythroid progenitors and only gp55-P induces Epo independence in Epo-dependent cell lines. Using chimeric gp55 P/A proteins, we extend earlier work showing that the transmembrane sequence determines the capacity of gp55 proteins to differentially activate EpoR signaling. We discuss the possibilities for different signaling capacities of gp55-A and -P in fetal liver and bone marrow-derived erythroid progenitor cells.

scholarly journals Bone Benefits of Fish Oil Supplementation Depend on its EPA and DHA Content

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2701
Author(s):  
Haissam Abou-Saleh ◽  
Allal Ouhtit ◽  
Ganesh V. Halade ◽  
Md Mizanur Rahman
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Fish Oil ◽  
Signaling Pathways ◽  
Dietary Intervention ◽  
High Dose ◽  
Chow Diet ◽  
Bone Resorption Marker ◽  
Mineral Density

The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%–4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.

scholarly journals Role of Erythropoietin Receptor Signaling in Parvovirus B19 Replication in Human Erythroid Progenitor Cells

2010 ◽  
Vol 84 (23) ◽  
pp. 12385-12396 ◽  
Author(s):  
Aaron Yun Chen ◽  
Wuxiang Guan ◽  
Sai Lou ◽  
Zhengwen Liu ◽  
Steve Kleiboeker ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Ex Vivo ◽  
Virus Entry ◽  
Parvovirus B19 ◽  
Erythropoietin Receptor ◽  
Receptor Expression ◽  
Janus Kinase ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

ABSTRACT Parvovirus B19 (B19V) infection is highly restricted to human erythroid progenitor cells. Although previous studies have led to the theory that the basis of this tropism is receptor expression, this has been questioned by more recent observation. In the study reported here, we have investigated the basis of this tropism, and a potential role of erythropoietin (Epo) signaling, in erythroid progenitor cells (EPCs) expanded ex vivo from CD34+ hematopoietic cells in the absence of Epo (CD36+/Epo− EPCs). We show, first, that CD36+/Epo− EPCs do not support B19V replication, in spite of B19V entry, but Epo exposure either prior to infection or after virus entry enabled active B19V replication. Second, when Janus kinase 2 (Jak2) phosphorylation was inhibited using the inhibitor AG490, phosphorylation of the Epo receptor (EpoR) was also inhibited, and B19V replication in ex vivo-expanded erythroid progenitor cells exposed to Epo (CD36+/Epo+ EPCs) was abolished. Third, expression of constitutively active EpoR in CD36+/Epo− EPCs led to efficient B19V replication. Finally, B19V replication in CD36+/Epo+ EPCs required Epo, and the replication response was dose dependent. Our findings demonstrate that EpoR signaling is absolutely required for B19V replication in ex vivo-expanded erythroid progenitor cells after initial virus entry and at least partly accounts for the remarkable tropism of B19V infection for human erythroid progenitors.

The Erythropoiesis Stimulating Agent Omontys/Peginesatide up-Modulates Erythroid Progenitor Formation, and Cell Surface Erythropoietin Receptor Levels.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2089-2089
Author(s):  
Rakesh Verma ◽  
Jennifer M Green ◽  
Karen Leu ◽  
Richard B Mortensen ◽  
Peter R. Young ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Surface ◽  
Ex Vivo ◽  
Erythropoietin Receptor ◽  
Cell Surface Expression ◽  
Dialysis Patients ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Murine Bone Marrow ◽  
Erythroid Development

Abstract Abstract 2089 Peginesatide is a peptide-based erythropoietin receptor (EPOR) agonist with recent FDA approval for treating the anemia of chronic kidney disease among adult dialysis patients. Although peginesatide exhibits a 47.9h half-life when given IV in dialysis patients, it is administered once-monthly. Taken together, this predicts that additional functional properties contribute to peginesatide's durable erythropoiesis stimulating activity. Here we report on three such properties. During ex vivo murine bone marrow erythroid development, compared directly to rHuEPO, peginesatide first enhanced KitposCD71pos progenitor cell expansion (including KitposCD71lowCD36posCD13pos erythromyelo- progenitors). Second, peginesatide exhibited a 1300 minute EPOR residence time vs. 77 minutes for rHuEPO. Third, the culture of EPO-dependent human UT7epo cells in peginesatide led to substantial EPOR up-modulation, as well as an apparent lessening of the processing of mature EPOR's. Furthermore, in studies that compared peginesatide vs. rHuEPO effects on the erythroid development of human bone marrow-derived CD34pos progenitors, the following differences were observed. At days 6–10 of culture, peginesatide gave rise to increased frequencies (up to 200% as compared to rHuEPO) of KitposCD71pos co-positive erythroid progenitors. At early stages (d2-d4), cell-surface EPOR levels also were elevated among progenitors expanded in peginesatide. When levels of CD13posCD36pos co-positive cells were analyzed, frequencies of these erythromyelo-progenitors also were heightened up to three-fold. Analyses of cultures at later time-points (eg, d10 of culture) indicated that peginesatide and rHuEPO supported the formation of GPAhigh erythroblasts at similarly high frequencies. In addition, cytospin analyses revealed morphological distinctions for multicellular proerythroblast complexes formed in peginesatide. Peginesatide's persistent erythropoietic activity allowing for once-monthly dosing therefore is likely to involve novel effects on erythromyelo-progenitor recruitment, and increased EPOR cell surface expression including apparent increases in relative levels of full-length EPOR forms. Disclosures: Green: Affymax, Inc.: Employment. Leu:Affymax, Inc.: Employment. Mortensen:Affymax, Inc.: Employment. Young:Affymax, Inc.: Prior employment Other. Schatz:Affymax, Inc.: Employment. Wojchowski:Affymax, Inc.: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Increased erythropoietin-receptor expression on CD34-positive bone marrow cells from patients with chronic myeloid leukemia

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 642-649
Author(s):  
AW Wognum ◽  
G Krystal ◽  
CJ Eaves ◽  
AC Eaves ◽  
PM Lansdorp
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Erythropoietin Receptor ◽  
Receptor Expression ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Normal Individuals ◽  
Marrow Cells

Erythropoietin-receptor (EpR) expression on bone marrow cells from normal individuals and from patients with chronic myeloid leukemia (CML) was examined by multiparameter flow cytometry after stepwise amplified immunostaining with biotin-labeled Ep, streptavidin- conjugated R-phycoerythrin, and biotinylated monoclonal anti-R- phycoerythrin. This approach allowed the detection of EpR-positive cells in all bone marrow samples studied. Most of the EpR-positive cells in normal bone marrow were found to be CD45-dull, CD34-negative, transferrin-receptor-positive and glycophorin-A-intermediate to - positive. This phenotype is characteristic of relatively mature erythroid precursors, ie, colony-forming units-erythroid and erythroblasts recognizable by classic staining procedures. Approximately 5% of normal EpR-positive cells displayed an intermediate expression of CD45, suggesting that these represented precursors of the CD45-dull EpR-positive cells. Some EpR-positive cells in chronic myeloid leukemia (CML) bone marrow had a phenotype similar to the major EpR-positive phenotype in normal bone marrow, ie, CD34-negative and CD45-dull. However, there was a disproportionate increase in the relative number of EpR-positive/CD45-intermediate cells in CML bone marrow. Even more striking differences between normal individuals and CML patients were observed when EpR-expression on CD34-positive marrow cells was analyzed. Very few EpR-positive cells were found in the CD34- positive fraction of normal bone marrow, whereas a significant fraction of the CD34-positive marrow cells from five of five CML patients expressed readily detectable EpR. These findings suggest that control of EpR expression is perturbed in the neoplastic clone of cells present in patients with CML. This may be related to the inadequate output of mature red blood cells typical of CML patients and may also be part of a more generalized perturbation in expression and/or functional integrity of other growth factor receptors on CML cells.

scholarly journals Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lingxian Yi ◽  
Yue Ju ◽  
Ying He ◽  
Xiushan Yin ◽  
Ye Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Intraperitoneal Injection ◽  
Vehicle Group ◽  
High Dose ◽  
Micro Ct ◽  
Aged Rats ◽  
Short Term ◽  
Age Related ◽  
Senescence Associated Genes

Abstract Background Age-related bone loss plays a vital role in the development of osteoporosis and osteoporotic fracture. Bone marrow stromal cell (BMSC) senescence is highly associated with osteoporosis and limits the application of BMSCs in regenerative medicine. Hypoxia is an essential component for maintaining the normal physiology of BMSCs. We have reported that activation of hypoxia-induced factor by deletion of von Hippel-Lindau gene in osteochondral progenitor cells protected mice from aging-induced bone loss. However, whether pharmacologically manipulation of hypoxic niche would attenuate age-related bone loss and dysfunction of BMSCs is not well understood. Methods Twelve-month-old Sprague-Dawley rats were used as an aged model and were intraperitoneally injected with Desferal® (20, 60 mg/kg weight or vehicle), three times a week for a continuous 8-week period. Two-month-old young rats were set as a reference. After 8 weeks, micro-CT and HE staining were performed to determine the effect of Desferal® on bone loss. In order to investigate the effects of Desferal® on BMSC senescence, 12-month-old rats were treated with high-dose Desferal® (60 mg/kg weight) daily for 10 days. BMSCs were isolated and evaluated using CCK-8 assay, colony-forming cell assay, cell differentiation assay, laser confocal for reactive oxygen species (ROS) level, senescence-associated β-galactosidase (SA-β-gal) staining, and molecular expression test for stemness/senescence-associated genes. Results Micro-CT and HE staining showed that high-dose Desferal® significantly prevented bone loss in aged rats. Compared with vehicle group, the ex vivo experiments showed that short-term Desferal® administration could promote the potential of BMSC growth (proliferation and colony formation ability) and improve the rebalance of osteogenic and adipogenic differentiation, as well as rejuvenate senescent BMSCs (ROS level and SA-β-gal staining) and revise the expression of stemness/senescence-associated genes. The potential of BMSCs from 12M-H-Desferal® group at least partly revised to the level close to 2-month-old group. Conclusions The current study suggested that Desferal®, an iron-chelating agent, could alleviate age-related bone loss in middle-aged rats. Meanwhile, we found that short-term intraperitoneal injection of Desferal® partly rejuvenate BMSCs from aged rats. Overall, we demonstrated a novel role of Desferal® in rejuvenating aged BMSCs and preventing age-related bone loss.

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