Cited by 777Bone Metabolism and DiseasesAxon Guidance and Neuronal SignalingMedicinal Plant Pharmacodynamics Research

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Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis

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Zhao, Chen, Irie, Naoko, Takada, Yasunari, Shimoda, Kouji, Miyamoto, Takeshi, Nishiwaki, Toru, Suda, Toshio, Matsuo, Koichi·2006·Cell Metabolism

DOI 10.1016/j.cmet.2006.05.012

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Abstract

Bone homeostasis requires a delicate balance between the activities of bone-resorbing osteoclasts and bone-forming osteoblasts. Various molecules coordinate osteoclast function with that of osteoblasts; however, molecules that mediate osteoclast-osteoblast interactions by simultaneous signal transduction in both cell types have not yet been identified. Here we show that osteoclasts express the NFATc1 target gene Efnb2 (encoding ephrinB2), while osteoblasts express the receptor EphB4, along with other ephrin-Eph family members. Using gain- and loss-of-function experiments, we demonstrate that reverse signaling through ephrinB2 into osteoclast precursors suppresses osteoclast differentiation by inhibiting the osteoclastogenic c-Fos-NFATc1 cascade. In addition, forward signaling through EphB4 into osteoblasts enhances osteogenic differentiation, and overexpression of EphB4 in osteoblasts increases bone mass in transgenic mice. These data demonstrate that ephrin-Eph bidirectional signaling links two major molecular mechanisms for cell differentiation--one in osteoclasts and the other in osteoblasts--thereby maintaining bone homeostasis.

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Retracted

Authors: Zhao, C., Irie, N., Takada, Y., Shimoda, K., Miyamoto, T., Nishiwaki, T., Suda, T., & Matsuo, K.
Affiliations: Keio University (JP)
Corresponding author: Matsuo, Koichi
ORCID: Zhao, Chen
Irie, Naoko
Miyamoto, Takeshi
Nishiwaki, Toru
Suda, Toshio
Matsuo, Koichi
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2006-08
Volume: 4
Issue: 2
Pages: 111-121
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2006.05.012
OpenAlex: W2026387061
Cited by: 777
References: 56
Citations by year: 2026: 25 · 2025: 25 · 2024: 23 · 2023: 34 · 2022: 35 · 2021: 45 · 2020: 49 · 2019: 33 · 2018: 42 · 2017: 42 · 2016: 47 · 2015: 39 · 2014: 46 · 2013: 40 · 2012: 59
FWCI: 15.54
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2578 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
Keywords: ephrin-B2, EphB4, bidirectional signaling, bone homeostasis, osteoclastogenesis, osteogenic differentiation, osteoblast-osteoclast interaction, NFATc1, c-fos, bone mass, Eph/ephrin signaling
MeSH terms: Animals, Base Sequence, Bone and Bones, Cell Differentiation, Cells, Cultured, Homeostasis, Mice, Transgenic, Molecular Sequence Data, Osteoblasts, Osteoclasts, Signal Transduction, Up-Regulation, Proto-Oncogene Proteins c-fos, Receptor, EphB4, Ephrin-B2, NFATC Transcription Factors, Mice

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Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis

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