ArticleThe Journal of biological chemistry2009
Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 173 citations in OpenAlex.
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- Bi-allelic EPHA2 mutations cause dysosteosclerosis by inhibiting osteoclastogenesis and enhancing osteoblastogenesis.Bone research · 2026Article
- Identification of ephrin-A1-EphA2 signalling as a potential target for fracture prevention.Nature communications · 2026Article
- The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies.International journal of obesity (2005) · 2026Review
- Sex-specific transcriptomic profiling reveals key players in bone loss associated with Alzheimer's disease.GeroScience · 2025Article
- EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.Cancer cell international · 2025Article
- Fibronectin-dependent integrin signaling drives EphA2 expression in vascular smooth muscle cells.American journal of physiology. Cell physiology · 2025Article
- Regulation of Osteoblast Differentiation by miR-214 and miR-206 Through EphrinA2 Signaling: Emerging Therapeutic Insights in Orthodontic Tooth Movement.International journal of molecular and cellular medicine · 2025Review
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.Journal of molecular medicine (Berlin, Germany) · 2024Review
- EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma.Cancer research communications · 2023Article
- Review
- Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.Cancer science · 2023Review
- Extracellular Vesicles in Bone Remodeling and Osteoporosis.Advances in experimental medicine and biology · 2023Review
- Geometric Control of Cell Behavior by Biomolecule Nanodistribution.ACS biomaterials science & engineering · 2022Article
- Neuronal Guidance Molecules in Bone Remodeling and Orthodontic Tooth Movement.International journal of molecular sciences · 2022Review
- Lipopolysaccharides affect compressed periodontal ligament cells via Eph-ephrin signaling.Oral diseases · 2022Article
- A Novel EphA4 Signaling-Based Therapeutic Strategy for Osteoarthritis in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Exosomes as mediators of intercellular crosstalk in metabolism.Cell metabolism · 2021Review
- A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement.International journal of molecular sciences · 2021Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone is remodeled constantly throughout life by bone-resorbing osteoclasts and bone-forming osteoblasts. To maintain bone volume and quality, differentiation of osteoclasts and osteoblasts is tightly regulated through communication between and within these two cell lineages. Previously we reported that cell-cell interaction mediated by ephrinB2 ligand on osteoclasts and EphB4 receptor on osteoblasts generates bidirectional anti-osteoclastogenic and pro-osteoblastogenic signals into respective cells and presumably facilitates transition from bone resorption to bone formation. Here we show that bidirectional ephrinA2-EphA2 signaling regulates bone remodeling at the initiation phase. EphrinA2 expression was rapidly induced by receptor activator of NF-kappaB ligand in osteoclast precursors; this was dependent on the transcription factor c-Fos but independent of the c-Fos target gene product NFATc1. Receptor EphA2 was expressed in osteoclast precursors and osteoblasts. Overexpression experiments revealed that both ephrinA2 and EphA2 in osteoclast precursors enhanced differentiation of multinucleated osteoclasts and that phospholipase Cgamma2 may mediate ephrinA2 reverse signaling. Moreover, ephrinA2 on osteoclasts was cleaved by metalloproteinases, and ephrinA2 released in the culture medium enhanced osteoclastogenesis. Interestingly, differentiation of osteoblasts lacking EphA2 was enhanced along with alkaline phosphatase, Runx2, and Osterix expression, indicating that EphA2 on osteoblasts generates anti-osteoblastogenic signals presumably by up-regulating RhoA activity. Therefore, ephrinA2-EphA2 interaction facilitates the initiation phase of bone remodeling by enhancing osteoclast differentiation and suppressing osteoblast differentiation.
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Registered trials
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.