The hepcidin regulator erythroferrone is a new member of the erythropoiesis-iron-bone circuitry.
Animals
Bone Development
/ genetics
Bone Morphogenetic Proteins
/ metabolism
Bone and Bones
/ metabolism
Cells, Cultured
Cytokines
/ genetics
Disease Models, Animal
Erythroblasts
Erythropoiesis
Hepcidins
Male
Mice, Inbred C57BL
Muscle Proteins
/ genetics
Osteoblasts
/ metabolism
beta-Thalassemia
/ genetics
bone formation
erythroferrone
medicine
mouse
osteoporosis
thalassemia
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
18 05 2021
18 05 2021
Historique:
received:
08
03
2021
accepted:
17
05
2021
pubmed:
19
5
2021
medline:
27
10
2021
entrez:
18
5
2021
Statut:
epublish
Résumé
Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis. To address whether ERFE functions also in bone and whether the mechanism of ERFE action in bone involves BMPs, we utilize the We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34002695
doi: 10.7554/eLife.68217
pii: 68217
pmc: PMC8205482
doi:
pii:
Substances chimiques
Bone Morphogenetic Proteins
0
Cytokines
0
Erfe protein, mouse
0
Hepcidins
0
Muscle Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK090554
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK127004
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG071870
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG060917
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107670
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK009055
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113627
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095112
Pays : United States
Informations de copyright
© 2021, Castro-Mollo et al.
Déclaration de conflit d'intérêts
MC, SG, MR, MF, AG, MP, CC, VS, CC, SK, EN, RF, SR, DL, TY, YG No competing interests declared, VO, HH is affiliated with Intrinsic Lifesciences, LLC. The author has no other competing interests to declare. MZ Deputy editor, eLife
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