Evidence map›Paper›PMID 34002695›Full record

ArticleeLife2021

The hepcidin regulator erythroferrone is a new member of the erythropoiesis-iron-bone circuitry.

Melanie Castro-Mollo, Sakshi Gera, Marc Ruiz-Martinez, Maria Feola, Anisa Gumerova, Marina Planoutene, Cara Clementelli, Veena Sangkhae, Carla Casu, Se-Min Kim and 9 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Thalassaemia.Nature reviews. Disease primers · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022
    Review
  13. The mutual crosstalk between iron and erythropoiesis.International journal of hematology · 2022
    Review
  14. Iron Mining for Erythropoiesis.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 1 country.

Melanie Castro-Mollo *Division of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
Sakshi Gera *The Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.ORCID 0000-0002-1615-6259
Marc Ruiz-MartinezDivision of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
Maria FeolaDivision of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
Anisa GumerovaThe Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Marina PlanouteneDivision of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
Cara ClementelliDivision of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
Veena SangkhaeCenter for Iron Disorders, University of California, Los Angeles (UCLA), Los Angeles, United States.
Carla CasuDepartment of Pediatrics, Division of Hematology, and Penn Center for Musculoskeletal Disorders, Children's Hospital of Philadelphia (CHOP), University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States.
Se-Min KimThe Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Vaughn OstlandIntrinsic Lifesciences, LLC, LaJolla, United States.
Huiling HanIntrinsic Lifesciences, LLC, LaJolla, United States.
Elizabeta NemethCenter for Iron Disorders, University of California, Los Angeles (UCLA), Los Angeles, United States.
Robert FlemingDepartment of Pediatrics, Saint Louis University School of Medicine, St Louis, United States.
Stefano RivellaDepartment of Pediatrics, Division of Hematology, and Penn Center for Musculoskeletal Disorders, Children's Hospital of Philadelphia (CHOP), University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States.
Daria LiznevaThe Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Tony YuenThe Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Mone ZaidiThe Mount Sinai Bone Program, Departments of Medicine and Pharmacological Sciences, and Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, United States.
Yelena GinzburgDivision of Hematology Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States.ORCID 0000-0002-3496-3783
Icahn School of Medicine at Mount Sinai · USChildren's Hospital of Philadelphia · USIntrinsic LifeSciences (United States) · USUniversity of California, Los Angeles · USSaint Louis University · US

Funding

Targeting FSH for the Therapy of Osteoporosis, Obesity and NeurodegenerationU19AG060917 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Mone Zaidi · 2019 to 2026
$29.0M
Regulatory Role of Transferrin in Erythropoiesis and Iron MetabolismR01DK095112 · NIDDK · SAINT LOUIS UNIVERSITY · PI Robert E Fleming, Yelena Ginzburg · 2012 to 2026
$5.4M
Hepcidin therapy for iron overload and hematologic disordersR01DK090554 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI RIVELLA, STEFANO · 2010 to 2021
$5.2M
The Role of Erythroferrone in Regulating Bone Metabolism in Beta-ThalassemiaR01DK107670 · NIDDK · NEW YORK BLOOD CENTER · PI GINZBURG, YELENA, YUEN, TONY · 2015 to 2025
$4.5M
Proof-of-Concept and Mechanistic Studies to Repurpose Erectile Dysfunction Drugs for Elderly FemalesR01AG071870 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KIM, SE-MIN, YUEN, TONY · 2021 to 2025
$3.9M
Thyrotropin Receptor, Thyrotropin and Mechanisms of Bone LossR01DK113627 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DAVIES, TERRY FRANCIS, IQBAL, JAMEEL Z · 2017 to 2020
$2.8M
Iron and Pregnancy: Regulatory Mechanisms and Adverse OutcomesK01DK127004 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SANGKHAE, VEENA · 2021 to 2025
$761k
MOLECULAR &BIOCHEMICAL ANALYSIS OF PKD1 CANDIDATE GENESF32DK009055 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI WATNICK, TERRY J · 1994 to 1996
–
NIA NIH HHS R01 AG071870NIA NIH HHS U19 AG060917NIDDK NIH HHS F32 DK009055NIDDK NIH HHS K01 DK127004NIDDK NIH HHS R01 DK090554NIDDK NIH HHS R01 DK095112NIDDK NIH HHS R01 DK107670NIDDK NIH HHS R01 DK113627
6 · The paper itself

Abstract

Background: Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. Methods: To address whether ERFE functions also in bone and whether the mechanism of ERFE action in bone involves BMPs, we utilize the Results: We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression. Conclusions: Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in β-thalassemia. Funding: YZG acknowledges the support of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK107670 to YZG and DK095112 to RF, SR, and YZG). MZ acknowledges the support of the National Institute on Aging (U19 AG60917) and NIDDK (R01 DK113627). TY acknowledges the support of the National Institute on Aging (R01 AG71870). SR acknowledges the support of NIDDK (R01 DK090554) and Commonwealth Universal Research Enhancement (CURE) Program Pennsylvania.

Indexed as

Animalsbeta-ThalassemiaBone and BonesBone DevelopmentBone Morphogenetic ProteinsCells, CulturedCytokinesDisease Models, AnimalErythroblastsErythropoiesisHepcidinsMaleMiceMice, Inbred C57BLMuscle ProteinsOsteoblastsBone Morphogenetic ProteinsCytokinesErfe protein, mouseHepcidinsMuscle Proteinsbone formationerythroferronemedicinemouseosteoporosisthalassemia

Identifiers

PMID34002695
PMCPMC8205482
OpenAlexW3152528733

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.