title: Spatial and temporal localization of WNT signaling proteins in a mouse model of distraction osteogenesis.
abstract: While the surgical procedure of distraction osteogenesis (DO) is very successful in the treatment of orthopedic conditions, its major limitation of slow bone formation in the distracted gap has prompted numerous attempts to understand and accelerate this slow bone formation. Interestingly, WNT/FZD signaling has been identified as a critical pathway in mediating bone formation and regeneration but has not yet been studied in the context of DO. The objective of this study was to determine the spatial and temporal localization of endogenous WNT signaling proteins at various times of bone formation in a wild-type mouse model of DO. In this study, the DO protocol performed on mice consisted of three phases: latency (5 days), distraction (12 days), and consolidation (34 days). Our immunohistochemical findings of distracted bone specimens show an increased expression of WNT ligands (WNT4 and WNT10A), receptors (FZD1 and 2, LRP5 and 6), β-catenin, and pathway antagonizers (DKK1; CTBP1 and 2; sFRP1, 2, and 4) during the distraction phase, which were then down-regulated during consolidation. This is the first published report to show an activation of the WNT pathway in DO and could help identify WNT as a potential therapeutic target in accelerating bone regeneration during DO.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: Bahar
authors.initials: B
authors.lastname: Kasaai
authors.forename: Pierre
authors.initials: P
authors.lastname: Moffatt
authors.forename: Loai
authors.initials: L
authors.lastname: Al-Salmi
authors.forename: Dominique
authors.initials: D
authors.lastname: Lauzier
authors.forename: Lucie
authors.initials: L
authors.lastname: Lessard
authors.forename: Reggie C
authors.initials: RC
authors.lastname: Hamdy
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D019857:Osteogenesis, Distraction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D005819:Genetic Markers; D051153:Wnt Proteins