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Erythroferrone Modulates Osteoblast-Osteoclast Crosstalk During Bone Remodeling
Pinanong Na-Phatthalung1,2, Gabrielle van Caloen1,2, Marina Planoutene1
1Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Biorxiv : the Preprint Server for Biology
|May 18, 2026
Summary
Osteoclast-derived erythroferrone (ERFE) is crucial for maintaining bone mass by regulating bone resorption. Loss of ERFE in osteoclasts leads to increased osteoclastogenesis and net bone loss, highlighting its osteoprotective role.
Area of Science:
- Bone Biology
- Endocrinology
- Hematopoiesis
Background:
- Erythroferrone (ERFE) regulates iron homeostasis by inhibiting hepcidin.
- ERFE is expressed in bone cells, and its global loss affects bone mass.
- The specific role of ERFE in osteoblasts versus osteoclasts is unclear.
Purpose of the Study:
- To investigate the role of osteoblast-derived ERFE in bone homeostasis.
- To determine the contribution of osteoclast-derived ERFE to bone mass regulation.
- To elucidate the mechanism by which ERFE influences osteoblast-osteoclast communication.
Main Methods:
- Generated osteoblast-selective ERFE knockout mice (Erfefl/fl; Col2.3-Cre).
- Compared bone mineral density (BMD) and osteoclast numbers in mutant and control mice.
- Utilized in vitro co-culture systems of osteoblasts and osteoclasts to study ERFE's cell-specific effects.
Main Results:
- Osteoblast-specific ERFE deletion did not cause bone loss; instead, it enhanced BMD during anabolic stress.
- Loss of ERFE in osteoblasts did not increase osteoclast numbers in vivo.
- ERFE loss in osteoblasts induced ERFE expression in osteoclasts in vitro.
- Osteoclastogenesis was induced only when ERFE was lost in osteoclasts during co-culture.
Conclusions:
- Osteoblast-derived ERFE is not responsible for the bone loss observed in global ERFE knockout mice.
- Osteoclast-derived ERFE is a critical regulator of osteoclastogenesis and bone mass.
- Loss of osteoclast ERFE leads to net bone loss due to enhanced bone resorption.
- ERFE from osteoclasts modulates communication between osteoblasts and osteoclasts to maintain bone homeostasis.
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