ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2014
Ephrin B2/EphB4 mediates the actions of IGF-I signaling in regulating endochondral bone formation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Insights into the mechanism of vascular endothelial cells on bone biology.Bioscience reports · 2021Pooled it
- EphB4-decorated biomimetic nanoparticles enhance osteoclast targeting and therapeutic effect in osteoporosis.Journal of nanobiotechnology · 2026Article
- 3D-printed triboelectric scaffolds for fabricating BMSC-derived cartilage to repair bone defects and promote endochondral ossification.Bioactive materials · 2026Article
- Identification of ephrin-A1-EphA2 signalling as a potential target for fracture prevention.Nature communications · 2026Article
- Parathyroid Hormone as a Modulator of Skeletal Muscle: Insights into Bone-Muscle and Nerve-Muscle Interactions.International journal of molecular sciences · 2025Review
- Fracture healing: cellular mechanisms and impact of parathyroid hormone and its analogs.Frontiers in endocrinology · 2025Review
- The Crosstalk Between Cartilage and Bone in Skeletal Growth.Biomedicines · 2024Review
- EphrinB2-EphB4 Signaling in Neurooncological Disease.International journal of molecular sciences · 2022Review
- Loading of erythropoietin on biphasic calcium phosphate bioceramics promotes osteogenesis and angiogenesis by regulating EphB4/EphrinB2 molecules.Journal of materials science. Materials in medicine · 2022Article
- Spatial Organization of Osteoclastic Coupling Factors and Their Receptors at Human Bone Remodeling Sites.Frontiers in molecular biosciences · 2022Article
- Anabolic actions of PTH in murine models: two decades of insights.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Sexual dimorphic impact of adult-onset somatopause on life span and age-induced osteoarthritis.Aging cell · 2021Article
- Effects of GH/IGF axis on bone and cartilage.Molecular and cellular endocrinology · 2021Review
- Eph-Ephrin Signaling Mediates Cross-Talk Within the Bone Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Ablation of Ephrin B2 in Col2 Expressing Cells Delays Fracture Repair.Endocrinology · 2020Article
- Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption.International journal of molecular sciences · 2020Review
- Ephrin/Eph receptor interaction facilitates macrophage recognition of differentiating human erythroblasts.Haematologica · 2020Article
- Article
- Icariin Alleviates Glucocorticoid-Induced Osteoporosis through EphB4/Ephrin-B2 Axis.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Changes in ephrin gene expression during bone healing identify a restricted repertoire of ephrins mediating fracture repair.Histochemistry and cell biology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ephrin B2/EphB4 mediates interactions among osteoblasts (OBs), osteoclasts (OCLs), and chondrocytes to regulate their differentiation. We investigated the role of ephrin B2/EphB4 signaling in mediating the anabolic effects of insulin-like growth factor-I (IGF-I) and parathyroid hormone (PTH) on those cells and overall endochondral bone formation. Immunohistochemistry demonstrated that the expression of ephrin B2 in OBs, OCLs, and osteocytes, and the expression of EphB4 in OBs and osteocytes was dramatically decreased in global IGF-I knockout mice. Inactivation of EphB4 by EphB4 small, interfering RNA (siRNA) in cultured bone marrow stromal cells significantly decreased the mRNA levels of OB differentiation markers and abolished the stimulatory effects of IGF-I on these markers. Blocking the interaction of EphB4 and ephrin B2 in the OB-OCL cocultures with the EphB4 specific peptide TNYL-RAW or deletion of ephrin B2 in OCL prior to coculture led to fewer and smaller tartrate-resistant acid phosphatase (TRAP)-positive cells, decreased expression of OB differentiation markers, and blunted response to IGF-I for both OCL and OB differentiation. In the growth plate, both ephrin B2 and EphB4 are expressed in late stage proliferating and prehypertrophic chondrocytes, and their expression was decreased in mice lacking the IGF-I receptor specifically in chondrocytes. In vitro, blocking the interaction of EphB4 and ephrin B2 in chondrogenic ATDC5 cells with TNYL-RAW significantly decreased both basal and IGF1-induced expression of type II and type X collagen. In the cocultures of ATDC5 cells and spleen cells (osteoclast precursors), TNYL-RAW decreased the numbers of TRAP-positive cells and the expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and receptor activator of NF-κB (RANK), and blocked their stimulation by IGF-I. Our data indicate that IGF-I/IGF-IR signaling promotes OB, OCL, and chondrocyte differentiation via ephrin B2/EphB4 mediated cell-cell communication.
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Registered trials
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