title: Cartilage-specific deletion of ephrin-B2 in mice results in early developmental defects and an osteoarthritis-like phenotype during aging in vivo.
abstract: BACKGROUND
  Ephrins and their related receptors have been implicated in some developmental events. We have demonstrated that ephrin-B2 (EFNB2) could play a role in knee joint pathology associated with osteoarthritis (OA). Here, we delineate the in vivo role of EFNB2 in musculoskeletal growth, development, and in OA using a cartilage-specific EFNB2 knockout (EFNB2(Col2)KO) mouse model.
  
  
  METHODS
  EFNB2(Col2)KO was generated with Col2a1-Cre transgenic mice. The skeletal development was evaluated using macroscopy, immunohistochemistry, histomorphometry, radiology, densitometry, and micro-computed tomography. Analyses were performed at P0 (birth) and on postnatal days P15, P21, and on 8-week- and 1-year-old mice.
  
  
  RESULTS
  EFNB2(Col2)KO mice exhibited significant reduction in size, weight, length, and in long bones. At P0, the growth plates of EFNB2(Col2)KO mice displayed increased type X collagen, disorganized hyphertrophic zone, and decreased mineralization. At P15, mutant mice demonstrated a significant reduction in VEGF and TRAP at the chondro-osseous junction and a delay in the secondary ossification, including a decrease in bone volume and trabecular thickness. At P21 and 8 weeks old, EFNB2(Col2)KO mice exhibited reduced bone mineral density in the total skeleton, femur and spine. One-year-old EFNB2(Col2)KO mice demonstrated OA phenotypic features in both the knee and hip. By P15, 27 % of the EFNB2(Col2)KO mice developed a hip locomotor phenotype, which further experiments demonstrated reflected the neurological midline abnormality involving the corticospinal tract.
  
  
  CONCLUSIONS
  This in vivo study demonstrated, for the first time, that EFNB2 is essential for normal long bone growth and development and its absence leads to a knee and hip OA phenotype in aged mice.
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.
authors.forename: Gladys
authors.initials: G
authors.lastname: Valverde-Franco
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.|Faculty of Veterinary Medicine, Clinical Science, University of Montreal, Saint-Hyacinthe, QC, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lussier
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hum
authors.affiliation: Laboratory of Immunology, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Neurosciences Department, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.|Groupe de recherche sur le sytème nerveux central (GRSNC), Neurosciences Department, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.
authors.forename: Adjia
authors.initials: A
authors.lastname: Hamadjida
authors.affiliation: Neurosciences Department, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.|Groupe de recherche sur le sytème nerveux central (GRSNC), Neurosciences Department, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.
authors.forename: Numa
authors.initials: N
authors.lastname: Dancause
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Fahmi
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.|Division of Genetics and Development, Toronto Western Research Institute, University Health Network (UHN) and Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), 900 Saint-Denis, R11.412B, Montreal, QC, H2X 0A9, Canada. jm@martelpelletier.ca.
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
mesh_terms: D000375:Aging; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001846:Bone Development / Q000502:physiology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D036388:Ephrin-B2 / Q000172:deficiency*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D055114:X-Ray Microtomography
chemical_list: D036388:Ephrin-B2
keywords: Bone development; Ephrin-B2; Knockout mouse model; Osteoarthritis