ArticleMolecular and cellular biology2010
Ephrin B1 regulates bone marrow stromal cell differentiation and bone formation by influencing TAZ transactivation via complex formation with NHERF1.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 101 citations in OpenAlex.
- Identification of a global gene expression signature associated with the genetic risk of catastrophic fracture in iPSC-derived osteoblasts from Thoroughbred horses.Animal genetics · 2025Article
- Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.Biology · 2023Article
- Lack of Skeletal Effects in Mice with Targeted Disruptionof Prolyl Hydroxylase Domain 1 (Life (Basel, Switzerland) · 2022Article
- Neuronal Guidance Molecules in Bone Remodeling and Orthodontic Tooth Movement.International journal of molecular sciences · 2022Review
- T-cell factor 7L2 is a novel regulator of osteoblast functions that acts in part by modulation of hypoxia signaling.American journal of physiology. Endocrinology and metabolism · 2022Article
- The CMS19 disease model specifies a pivotal role for collagen XIII in bone homeostasis.Scientific reports · 2022Article
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- Targeted Deletion of theFrontiers in endocrinology · 2022Article
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- Eph-Ephrin Signaling Mediates Cross-Talk Within the Bone Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Hippo Signaling Pathway as a Central Mediator of Receptors Tyrosine Kinases (RTKs) in Tumorigenesis.Cancers · 2020Review
- EphrinB2 overexpression enhances osteogenic differentiation of dental pulp stem cells partially through ephrinB2-mediated reverse signaling.Stem cell research & therapy · 2020Article
- Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells.Journal of clinical medicine · 2020Review
- Novel Role for Claudin-11 in the Regulation of Osteoblasts via Modulation of ADAM10-Mediated Notch Signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Article
- Conditional disruption of theBone research · 2019Article
- Changes in ephrin gene expression during bone healing identify a restricted repertoire of ephrins mediating fracture repair.Histochemistry and cell biology · 2019Article
- LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin.Journal of cellular biochemistry · 2018Article
- The osteoprogenitor-specific loss of ephrinB1 results in an osteoporotic phenotype affecting the balance between bone formation and resorption.Scientific reports · 2018Article
- A novel miR17/protein tyrosine phosphatase-oc/EphA4 regulatory axis of osteoclast activity.Archives of biochemistry and biophysics · 2018Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced ephrin B1 in vivo and identified the molecular mechanism by which ephrin B1 reverse signaling regulates bone formation. Targeted deletion of the ephrin B1 gene in type 1alpha2 collagen-producing cells resulted in severe calvarial defects, decreased bone size, bone mineral density, and trabecular bone volume, caused by impairment in osterix expression and osteoblast differentiation. Coimmunoprecipitation of the TAZ complex with TAZ-specific antibody revealed a protein complex containing ephrin B1, PTPN13, NHERF1, and TAZ in bone marrow stromal (BMS) cells. Activation of ephrin B1 reverse signaling with soluble EphB2-Fc led to a time-dependent increase in TAZ dephosphorylation and shuttling from cytoplasm to nucleus. Treatment of BMS cells with exogenous EphB2-Fc resulted in a 4-fold increase in osterix expression as determined by Western blotting. Disruption of TAZ expression using specific lentivirus small hairpin RNA (shRNA) decreased TAZ mRNA by 80% and ephrin B1 reverse signaling-mediated increases in osterix mRNA by 75%. Knockdown of NHERF1 expression reduced basal levels of osterix expression by 90% and abolished ephrin B1-mediated induction of osterix expression. We conclude that locally produced ephrin B1 mediates its effects on osteoblast differentiation by a novel molecular mechanism in which activation of reverse signaling leads to dephosphorylation of TAZ and subsequent release of TAZ from the ephrin B1/NHERF1/TAZ complex to translocate to the nucleus to induce expression of the osterix gene and perhaps other osteoblast differentiation genes. Our findings provide strong evidence that ephrin B1 reverse signaling in osteoblasts is critical for BMS cell differentiation and bone formation.
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