Erythropoiesis, EPO, macrophages, and bone

Eggold, Joshua T.; Rankin, Erinn B.

doi:10.1016/j.bone.2018.03.014

Cited by 58 publications

(54 citation statements)

References 89 publications

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“…Erythropoiesis happens in human red bone marrow after kidneys responses to low levels of oxygen by releasing erythropoietin [35]. Erythropoiesis is a multi-step cellular course by which a primitive multipotent HSC experiences a series of differentiations resulting in production of erythroid lineage, undergoing erythroid progenitors (colony-forming unit erythroid [CFU-E] and burst-forming unit erythroid [BFU-E]), normoblasts, proerythroblasts, early basophilic erythroblasts, late basophilic erythroblasts, polychromatic erythroblasts, orthochromatic erythroblasts, reticulocytes, ultimately differentiating to mature erythrocytes [5,6]. Megakaryopoiesis occurs through a hierarchical series of progenitor cells, multipotent progenitor (MPP), common myeloid progenitor (CMP) and megakaryocyte-erythroid progenitor (MEP), megakaryocyte progenitor (MKP), ultimately differentiating to mature megakaryocytes [36].…”

Section: Discussionmentioning

confidence: 99%

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CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

Guo

Zhang

Yan

et al. 2020

Preprint

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Background: As members of the CT10 regulation of kinase (CRK) adaptor protein family, CRK-like (CRKL) and CRKII are involved in cell proliferation, survival, adhesion, migration and differentiation. However, the exact role and underlying mechanism of CRKL and CRKII in leukemic cell differentiation are still unknown. Methods: Quantitative real-time qPCR (qRT-PCR) was used to detect the expression levels of CRKL and CRKII in chronic myeloid leukemia (CML) patients and complete remission (CR) patients; Western blotting (WB) was used to measure the expression levels of CRKL and CRKII during hemin-induced erythroid differentiation of K562 cells; Benzidine staining, isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis, cDNA microarray assay, qRT-PCR and WB were used to examine the effects of CRKL and CRKII deregulation on erythroid and megakaryocyte differentiation of K562 cells; PD98059 was used to investigate the underlying mechanism of CRKL in erythropoiesis and megakaryopoiesis. Results: CRKL was found to be overexpressed in chronic myeloid leukemia (CML) patients compared with normal samples, while its expression level was lower in CR patients than in corresponding CML patients. The CRKL expression level was significantly decreased during the erythroid differentiation of K562 cells following hemin treatment. Moreover, CRKL downregulation promoted erythroid and megakaryocyte differentiation of K562 cells accompanied by increased expression level of the erythroid differentiation markers γ-globin, glycophorin (GPA) and the megakaryocyte differentiation markers CD41, CD61. Furthermore, gene microarray and iTRAQ quantitative proteomic analysis showed that CRKL downregulation increased hemoglobin (HB) molecules HBD, HBA1, HBA2, HBZ, HBE1, HBG1 and globin transcription factor 1 (GATA1), high-mobility group protein (HMGB2) expression levels. Mechanistically, CRKL inhibited erythroid and megakaryocyte differentiation of K562 cell via inactivating Raf/MEK/ERK/Elk-1 pathway. Conversely, CRKII was only slightly overexpressed in CML patients and had no effect on erythroid differentiation of K562 cells. Conclusions: Taken together, our results demonstrate that CRKL but not CRKII contributes to development, progression, erythropoiesis and megakaryopoiesis of CML, providing novel insights into effective diagnosis and therapy for CML patients.

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Section: Discussionmentioning

confidence: 99%

“…Erythropoiesis and megakaryopoiesis are important parts of hematopoiesis [3,4]. Normal erythropoiesis produces about 10 11 new red blood cells (RBCs) every day in an adult human through the commitment of hematopoietic stem cells into erythroid progenitors, which subsequently differentiate into mature RBCs [5,6].…”

Section: Introductionmentioning

confidence: 99%

CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

Guo

Zhang

Yan

et al. 2020

Preprint

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“…Of interest for skeletal tissue engineering, the pleiotropic capabilities of EPO include osteogenic and angiogenic potencies. (6)(7)(8)(9)(10) The studies coupling the EPO to bone healing reported that the use of EPO was supraphysiologic dosage and had potential harmful implication like high blood viscosity and consecutive thromboembolic events. Many researches shifted to the use of topical administration of EPO into the bone defect to improve the efficiency of EPO on the bone formation with minimal systemic effect.…”

Section: Discussionmentioning

confidence: 99%

“…The hormone Erythropoietin (EPO) has been used for treating anemia and its angiogenic effects are proven by several researches (8) . It regulates red blood cells generation in the bone marrow together with bone homeostasis (9) . EPO was proved to increase the expression of vascular endothelial growth factors (VEGFs) and bone morphogenetic protein (BMP 2) both play an essential role in vascular formation and the angiogenesis process ((10,11) .…”

Section: Introductionmentioning

confidence: 99%

Effects of Erythropoietin on The Healing of Calvarial Bone Defect

Ahmed

Elmagd

Khairy

et al. 2019

Egyptian Dental Journal

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Objectives To evaluate the effect of a single-dose local administration versus the systemic administration of Erythropoietin on bone healing in calvarial bone defectsMaterial & Methods Critical-size cranial osteotomy defects were created in 30 rabbits. The animals were randomly divided into 3 groups. The animals were randomly divided into 3 groups (n= 10 animals in each group). In the Group I, the bone defect was only filled with a collagen sponge soaked with erythropoietin. In the Group II, it was filled with a collagen sponge and erythropoietin injected systemically. While in the Group III, the defect was filled with a collagen sponge. The groups were further split in two for euthanasia 10-and 21-days post-surgery. New bone formation and neovascularization were evaluated by hematoxylin-eosin. For the 10-days samples, all the groups analyzed for area percent of blood vessels while on the 21-day samples, the area of new bone formation was calculated. Differences between groups were analyzed by one-way ANOVA.Results At 10 days post-surgery, the histological analysis showed that the erythropoietin Groups exhibited a significantly higher percentage of bone formation compared with the other Group. At 21 days post-surgery, a higher percentage of new bone was observed in the erythropoietin group. ConclusionsThe results suggest that both local and systemic administration of erythropoietin hormone encouraged the bone healing in critical-size calvarial defects in Rabbits.

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“…(4) It has been speculated that regulation of erythropoiesis and bone remodeling is coordinated in the hematopoietic stem cell niche. (5,6) This view is supported by both clinical and experimental observations as osteoporosis and fractures are more commonly observed in patients with anemia and polycythemia. Patients with thalassemia (7) or sickle cell disease (8) have low bone mass and increased risk of fractures, and the concomitant anemia is associated with high serum levels of EPO.…”

Section: Introductionmentioning

confidence: 88%

High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function: The MrOS Sweden Cohort

Kristjánsdóttir

Lewerin

Lerner

et al. 2019

Journal of Bone and Mineral Research

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Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean AE SD EPO was 11.5 AE 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = −0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function.

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Erythropoiesis, EPO, macrophages, and bone

Cited by 58 publications

References 89 publications

CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

CRKL but not CRKII Inhibits Erythropoiesis and Megakaryopoiesis of CML via Inactivating Raf/MEK/ERK/Elk-1 Pathway

Effects of Erythropoietin on The Healing of Calvarial Bone Defect

High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function: The MrOS Sweden Cohort

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