Effects of bone morphogenetic protein 2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits

• Published in: Oral surgery, oral medicine, oral pathology, oral radiology and endodontics oral medicine, oral pathology, oral radiology and endodontics, 2011-07, Vol.112 (1), p.50-57
• Main Authors: Long, Jie, MD, PhD, Li, Peng, MD, PhD, Du, Hong-ming, MD, PhD, Liu, Lei, MD, PhD, Zheng, Xiao-hui, MD, PhD, Lin, Yun-feng, MD, PhD, Wang, Hang, MD, PhD, Jing, Wei, MD, PhD, Tang, Wei, MD, PhD, Chen, Wei-hui, MD, PhD, Tian, Wei-dong, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Animals; Biological and medical sciences; Biomechanical Phenomena; Bone Density - genetics; Bone marrow; Bone Marrow Cells - virology; Bone mineral density; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - genetics; Callus; Cell Culture Techniques; Cell physiology; Computed tomography; Dentistry; Distraction osteogenesis; Feasibility Studies; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic Therapy; Genetic Vectors - genetics; Humans; Male; Mandible; Mandible - diagnostic imaging; Mandible - pathology; Mandible - surgery; Mandibles; Medical sciences; Mesenchymal Stromal Cells - virology; Mesenchyme; Mineralization, calcification; Molecular and cellular biology; Osteogenesis; Osteogenesis - genetics; Osteogenesis, Distraction - instrumentation; Osteogenesis, Distraction - methods; Otorhinolaryngology. Stomatology; Pliability; Rabbits; Radiography; Random Allocation; Recombinant Proteins - genetics; Skeleton and joints; Stem cells; Stress; Stress, Mechanical; Surgery; Time Factors; Transfection - methods; Transforming Growth Factor beta - genetics; Vertebrates: osteoarticular system, musculoskeletal system; X-Ray Microtomography
• ISSN: 1079-2104; 1528-395X
• DOI: 10.1016/j.tripleo.2010.09.065

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. Study design 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.