title: Effects of Wnt5a Haploinsufficiency on Bone Repair.
abstract: OBJECTIVE
  Wnt5a expression is upregulated during fracture repair and has previously been implicated as a potential regulator of skeletal development and bone mass accrual and maintenance. Our objective was to evaluate the function of Wnt5a in fracture healing.
  
  
  METHODS
  Femoral fracture experiments on Wnt5a and Wnt5a mice were carried out. To better understand the effect of the Wnt5a on bone repair, we evaluated radiographs using a previously validated qualitative scoring system and performed microcomputed tomography analyses. Histomorphometric analyses determined the temporal distribution of stroma, cartilage matrix, and woven bone in the fracture callus. Finally, we performed tartrate-resistant acid phosphatase (TRAP) immunohistochemical staining to visualize and quantify bone resorbing cells.
  
  
  RESULTS
  Radiographic evaluations at day 21 demonstrated significantly higher cortical remodeling and bridging parameters for the Wnt5a group compared with the Wnt5a group. The bone volume fraction by microcomputed tomography was also significantly increased in Wnt5a mice. Histological and histomorphometric analyses showed that although Wnt5a mice exhibit decreased cartilage matrix production at day 7 postfracture, they displayed increased residual cartilaginous callus at days 14 and 21 compared with the Wnt5a group. In addition, the total number of multinucleated tartrate-resistant acid phosphatase-positive cells was significantly lower in the Wnt5a group than in the Wnt5a group.
  
  
  CONCLUSIONS
  The data indicate that decreased Wnt5a signaling impaired proper fracture healing, possibly through decreased cartilaginous callus formation, and delayed cartilage matrix and mineralized tissue remodeling within the fracture callus.
authors.affiliation: Department of Orthopaedic Surgery, New England Musculoskeletal Institute, University of Connecticut Health Center, Farmington, CT.
authors.forename: Kari B
authors.initials: KB
authors.lastname: Clifton
authors.forename: David N
authors.initials: DN
authors.lastname: Paglia
authors.forename: Do Y
authors.initials: do Y
authors.lastname: Soung
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wolf
authors.forename: Isaac L
authors.initials: IL
authors.lastname: Moss
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology; D002146:Bony Callus / Q000378:metabolism / Q000503:physiopathology; D002356:Cartilage / Q000503:physiopathology; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D017102:Fracture Healing / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D057895:Haploinsufficiency; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011859:Radiography; D051153:Wnt Proteins / Q000235:genetics*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse