The effect of erythropoietin on bone

Rölfing, Jan Duedal

doi:10.3109/17453674.2013.869716

Cited by 10 publications

(13 citation statements)

References 91 publications

(134 reference statements)

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“…Osteoblastic human and mouse bone marrow stromal cells express Epor mRNA (10,32) and EPO-R protein. (32,33) The Epor mRNA expression increases with osteoblastic differentiation (10) and can be induced by EPO. (34) Expression of Epor mRNA has also been demonstrated in mouse osteoclast progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Moreover, single erythropoietin dosing facilitates clinical application and proved to be sufficient to improve the bone healing. (25,27,31) The histological outcomes showed that group II which received EPO as a systemic single dose were more effective on repairing the bone defects and can promote the osteogenesis and angiogenesis especially in the early stage of bone healing when compared with group III that did not received any EPO hormone.…”

Section: Discussionmentioning

confidence: 99%

“…This was in accordance with Previous studies that reported EPO could promote proliferation and induce to osteoblast, accelerate the growth of osteoblast and strengthen its osteogenesis function. (24,26,27,30,31) Furthermore, Omlor et al (27) , who use the single systemic EPO dose to promote bone healing in rabbits concluded that Initial single dosing with EPO was enough to increase bone healing substantially after 12 weeks of follow-up. They reported that the single application of EPO at early time point appears to be most effective and intraoperative administration as a single dose appears most attractive to improve the bone healing.…”

Section: Discussionmentioning

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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“…EPO is most similar to cytokines, which modulate growth and inflammation (Erbayraktar et al 2003). EPO is made up of about 60% protein and 40% carbohydrate (Rölfing 2014). Molecular weight of the EPO is 30.4 kDa (Jelkmann 2013).…”

Section: Structure and Synthesis Of Erythropoietinmentioning

confidence: 99%

“…During hypoxia, the EPO gene expression increases in the kidney peritubular fibroblasts via hypoxia-induced transcription factor, and EPO is subsequently released into the circulation (Rölfing 2014). Before the birth, the liver is a primary site of EPO production, in adults approximately 10% of EPO is synthesized by the liver (Dame et al 1998, Jelkmann 2007, Rankin et al 2007, Rölfing 2014, Zanjani et al 1977. Predominant expression of EPO occurs in kidneys and liver, though transcripts can be also found in other tissues, such as brain, heart, and lungs (Elliott and Sinclair 2012).…”

Section: Structure and Synthesis Of Erythropoietinmentioning

confidence: 99%

Pleiotropic effects of Erythropoietin. Influence of Erythropoietin on processes of mesenchymal stem cells differentiation

Zubareva¹,

Nadezhdin²,

Burda³

et al. 2019

RRP

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Structure and synthesis of Erythropoietin: Erythropoietin (EPO) is a glycoprotein hormone.Recombinant Erythropoietin (Epoetin): Human recombinant erythropoietin is characterised as a factor which stimulates differentiation and proliferation of erythroid precursor cells, and as a tissue protective factor.Anti-ischemic effects of recombinant Erythropoietin: Erythropoietin is one of the most perspective humoral agents which are involved in the preconditioning phenomenon.Erythropoietin receptors and signal transduction pathways: Erythropoietin effects on cells through their interconnection with erythropoietin receptors, which triggers complex intracellular signal cascades, such as JAK2/STAT signaling pathway, phosphatidylinositol 3-kinase (PI3K), protein kinase C, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB signaling pathways.Mechanisms of the effect of Erythropoietin on hematopoietic and non-hematopoietic cells and tissues: In addition to regulation of haemopoiesis, erythropoietin mediates bone formation as it has an effect on hematopoietic stem cells and osteoblastic niche, and this illustrates connection between the processes of haematopoiesis and osteopoiesis which take place in the red bone marrow.The effect of Erythropoietin on mesenchymal stem cells and process of bone tissue formation: Erythropoietin promotes mesenchymal stem cells proliferation, migration and differentiation in osteogenic direction. The evidence of which is expression of bone phenotype by cells under the influence of EPO, including activation of bone specific transcription factors Runx2, osteocalcin and bone sialoprotein.Conclusion: Erythropoietin has a pleiotropic effect on various types of cells and tissues. But the mechanisms which are involved in the process of bone tissue restoration via erythropoietin are still poorly understood.

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The effect of erythropoietin on bone

Cited by 10 publications

References 91 publications

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

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

Effects of Erythropoietin on The Healing of Calvarial Bone Defect

Pleiotropic effects of Erythropoietin. Influence of Erythropoietin on processes of mesenchymal stem cells differentiation

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