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

J Oral Maxillofac Surg. 2011 Nov;69(11):e446-55. doi: 10.1016/j.joms.2011.07.002.

Abstract

Purpose: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / analysis
  • Animals
  • Bone Density / drug effects
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Bone Regeneration / drug effects
  • Bone Remodeling / drug effects
  • Cell Count
  • Cranial Sutures / surgery*
  • Dogs
  • Drug Carriers
  • Drug Synergism
  • Fibrin Tissue Adhesive / therapeutic use
  • Fibroblasts / drug effects
  • Humans
  • Immunohistochemistry
  • Lactic Acid
  • Maxilla / surgery
  • Microscopy, Electron, Transmission
  • Osteoblasts / drug effects
  • Osteocytes / drug effects
  • Osteogenesis / drug effects*
  • Osteogenesis, Distraction / instrumentation
  • Osteogenesis, Distraction / methods*
  • Osteoprotegerin / therapeutic use*
  • Palate, Hard / surgery*
  • Pilot Projects
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Recombinant Proteins / therapeutic use
  • Time Factors
  • Transforming Growth Factor beta / therapeutic use*

Substances

  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Fibrin Tissue Adhesive
  • Osteoprotegerin
  • Recombinant Proteins
  • TNFRSF11B protein, human
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Alkaline Phosphatase