Synergistic enhancement of new bone formation by recombinant human bone morphogenetic protein-2 and osteoprotegerin in trans-sutural distraction osteogenesis: a pilot study in dogs.
OBJECTIVE
The previous decade has witnessed increasing emphasis on the technique of trans-sutural distraction osteogenesis (TSDO), a new and challenging procedure to reconstruct deficiencies in craniomaxillofacial bone. The purpose of this study was to determine if locally administered recombinant human bone morphogenetic protein-2 (BMP-2)/Poly(lactic-co-glycolic acid)/Fibrin sealant and recombinant human osteoprotegerin recombinant OPG fusion protein improves osteoblastogenesis and new bone formation by TSDO.


METHODS
Thirty-two dogs were divided into 4 groups: control, BMP-2, OPG, or BMP-2 plus OPG. Two dogs from each group were sacrificed at 1, 2, 4, and 6 weeks after initiating the DO protocol. Immunohistochemical, histomorphometric, and electron microscopic assessments were performed to investigate the effects of BMP-2 or OPG induced by TSDO.


RESULTS
The animals demonstrated significant overgrowth of the maxilla (control, 19.5 ± 2.61 mm; BMP-2, 19.9 ± 1.47 mm; OPG, 18.3 ± 1.2 mm; BMP-2 + OPG, 20.5 ± 2.65 mm). Histologically, the palatine suture widened dramatically within 2 weeks after distraction. Osteoblast number, trabecular thickness, content of alkaline phosphatase, and integrated optical density of BMP-2 increased obviously in the BMP-2 + OPG group (P < .05).


CONCLUSIONS
TSDO in growing dogs is a safe, well-tolerated technology. The study found that OPG alone did not improve bone regeneration, but that it acted synergistically with BMP-2 to increase recruitment of mesenchymal stem cells and led to a significant enhancement of bone formation and healing. The temporal pattern of BMP-2 expression is consistent with a role in the regulation of mechanical and biological interventions designed to promote bone regeneration.
Second Affiliated Hospital, Liaoning Medical College, Jinzhou, China. yaoyusheng700714@sina.com
Yusheng
Y
Yao
Guijun
G
Wang
Zhiying
Z
Wang
Chengyue
C
Wang
Haizhong
H
Zhang
Chunming
C
Liu
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002452:Cell Count; D003393:Cranial Sutures / Q000601:surgery*; D004285:Dogs; D004337:Drug Carriers; D004357:Drug Synergism; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid; D008437:Maxilla / Q000601:surgery; D046529:Microscopy, Electron, Transmission; D010006:Osteoblasts / Q000187:drug effects; D010011:Osteocytes / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction / Q000295:instrumentation / Q000379:methods*; D053244:Osteoprotegerin / Q000627:therapeutic use*; D021362:Palate, Hard / Q000601:surgery*; D010865:Pilot Projects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D053244:Osteoprotegerin; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase