title: Effects of bone morphogenetic protein 2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits.
abstract: OBJECTIVE
  We investigated the effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) on new bone formation during rapid-rate mandibular distraction osteogenesis. We also explored the feasibility of using local BMP-2 gene therapy to compensate for bad callus formation caused by a rapid distraction rate.
  
  
  METHODS
  Bone marrow mesenchymal stem cells (MSCs) from Japanese rabbits were transfected with adenovirus (adv)-BMP-2. The right mandibles of the rabbits were distracted after corticotomy. The distraction rate in group A was 0.8 mm/d. The distraction rate in group B was 2.4 mm/d, and the distraction gap was injected with adv-lacZ-transfected bone marrow MSCs. The distraction rate in group C was 2.4 mm/d, and the distraction gap was injected with adv-BMP-2-transfected bone marrow MSCs. New generation bone tissue in the distraction gap was analyzed by plain radiograph examinations, microfocus computerized tomography (micro-CT) examinations, and biomechanical tests at weeks 2, 4, and 8 of the consolidation period.
  
  
  RESULTS
  Radiographic and micro-CT examinations showed a better bone quality in group C compared with group A at weeks 2 and 4 of the consolidation period. There was no obvious new bone formation in group B. The trabecular parameters (trabecular thickness, trabecular number, volumetric bone mineral density at tissue, and bone volume fraction) were significantly higher in group C than in group A at weeks 2 and 4. At week 8, no significant difference were detected for all parameters except trabecular number between groups A and C. All biomechanical stress parameters were significantly higher in group C than in group A at week 4, and only peak stress was significantly different at week 8.
  
  
  CONCLUSIONS
  Gene therapy using rhBMP-2-modified MSCs promoted new bone formation during mandibular distraction osteogenesis, and effectively compensated for the detrimental effect of rapid distraction rate on new bone formation.
authors.affiliation: Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Long
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Hong-ming
authors.initials: HM
authors.lastname: Du
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zheng
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Wei-hui
authors.initials: WH
authors.lastname: Chen
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Tian
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000235:genetics; D001854:Bone Marrow Cells / Q000821:virology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D018929:Cell Culture Techniques; D005240:Feasibility Studies; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D059630:Mesenchymal Stem Cells / Q000821:virology; D010012:Osteogenesis / Q000235:genetics*; D019857:Osteogenesis, Distraction / Q000295:instrumentation / Q000379:methods*; D018583:Pliability; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2