title: Ephrin-B stimulation of calvarial bone formation.
abstract: BACKGROUND
  Ephrin-B2 on osteoclasts was reported to promote bone formation as part of homeostasis by activating the EphB4 tyrosine kinase receptor on osteoblasts. Little is known about the role of ephrin-B signaling to EphBs in developmental bone formation.
  
  
  RESULTS
  We observed expression of an ephrin-B2 LacZ chimeric allele in the periosteum, sutural bone fronts, and dura mater of embryonic and neonatal mice. Expression in the adult skull was confined to sutures, but was heavily upregulated at sites of bone injury. Culture of embryonic calvariae with soluble recombinant ephrin-B2/Fc doubled their bone content without altering suture width or overall skull morphology. Ephrin-B2/Fc also stimulated osteoblast marker gene expression in cultured MC3T3 preosteoblastic cells without the need for type 1 collagen-induced differentiation. EphB4 was absent in embryonic and adult skulls. However, EphB1 and EphB2, both physiological receptors for ephrin-Bs, were expressed at sites of osteogenesis, and EphB1 knockout mice displayed a reduction in calvarial bone content compared to controls.
  
  
  CONCLUSIONS
  These data support a role for ephrin-B2 in the development and healing of bone through activation of osteoblast-specific gene expression. EphB1 and EphB2 are likely candidates receptors for the ephrin-B2 in bone.
authors.affiliation: Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas 75246, USA. mdbenson@bcd.tamhsc.edu
authors.forename: M Douglas
authors.initials: MD
authors.lastname: Benson
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Opperman
authors.forename: Jan
authors.initials: J
authors.lastname: Westerlund
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Fernandez
authors.forename: Symone
authors.initials: S
authors.lastname: San Miguel
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
authors.forename: George
authors.initials: G
authors.lastname: Chenaux
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D036225:Receptor, EphB1 / Q000235:genetics / Q000378:metabolism; D036183:Receptor, EphB2 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D012886:Skull / Q000166:cytology / Q000196:embryology*
chemical_list: D000943:Antigens, Differentiation; D036388:Ephrin-B2; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D036225:Receptor, EphB1; D036183:Receptor, EphB2