title: Wnt/β-catenin signaling is required for distraction osteogenesis in rats.
abstract: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized.
  
  
  
  We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process. Animals in the experimental group received rrDkk1 injections (dose = 25 μg/kg) once daily during distraction period and every third day during consolidation stage (n = 48). Animals in the control group received saline under the same injection strategy (n = 48). Animals at different time points during DO process (1, 3, 6, 12 days after distraction, 10 days and 6 weeks after consolidation) were killed and tissues in the distraction region were harvested for radiography, dual energy X-ray absorptiometry, micro-computed tomography (micro-CT), and histological analyses.
  
  
  
  Most Wnt ligands, cofactors, receptors, and antagonists were widely expressed in the distraction callus and were significantly upregulated during DO process. After rrDkk1 administration, the majority of these factors were downregulated at the mRNA level, except sFRP and GSK-3β. At the protein level, both β-catenin and Lef-1 were also suppressed by rrDkk1. In the long term, restricted bone healing was observed in the distracted callus in the rrDkk1 injection group. These findings were confirmed by histological and micro-CT analyses.
  
  
  
  Our findings suggest that Wnt signaling participates in the process of DO, and clinical therapeutic approaches of DO may do well to avoid Wnt pathway suppression.
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: En
authors.initials: E
authors.lastname: Luo
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: Ruiye
authors.initials: R
authors.lastname: Bi
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: a State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases , West China Hospital of Stomatology, Sichuan University , Chengdu , China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zou
mesh_terms: D000818:Animals; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D019857:Osteogenesis, Distraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D060449:Wnt Signaling Pathway; D055114:X-Ray Microtomography; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin
keywords: Bone regeneration; Dkk1; Wnt signaling; distraction osteogenesis; tibia