Recombinant osteoprotegerin effects during orthodontic movement in a rat model

Eur J Orthod. 2016 Aug;38(4):379-85. doi: 10.1093/ejo/cjv056. Epub 2015 Aug 20.

Abstract

Background and objectives: Anchorage is one of the most challenging sides in orthodontics. The use of biological modulators that inhibit osteoclasts could be a solution to address these problems and provide new adjunctive approaches. The aim of this study was to assess the effectiveness of recombinant osteoprotegerin fusion protein (OPG-Fc) in orthodontic anchorage.

Materials and methods: Two groups of male Sprague-Dawley rats were utilized. The animals in the experimental group received twice-weekly injections with high dose of OPG-Fc (5.0mg/kg) in mesial and distal mucosa of the first molars, and those in the control group received no drugs. Right first maxillary molars were mesialized using a calibrated nickel-titanium spring connected to an anterior mini-screw. Tooth movement was measured by two blinded observers using scanned and magnified stone casts. Receptor activator of nuclear factor κB (RANK), run-related transcription factor 2 (Runx2), type I collagen, vimentin, matrix metalloproteinases 2 and 9, S100 protein and the putative mechanoproteins acid-sensing ion channel (ASIC2) and transient receptor potential vainilloid 4 (TRPV4) were evaluated using immunohistochemistry.

Results: OPG-Fc group showed an important decreased in mesial molar movement with only 52%, 31%, and 22% of the total mesial molar movement compared with control group at Days 7, 14, and 21, respectively (P < 0.001). RANK ligand and Runx2 positive cells were severely reduced after OPG-Fc treatment. Periodontal ligament architecture, cell arrangement, and immunohistochemical patter for vimentin, type I collagen and the mechanoproteins TRPV4 and ASIC2 were altered by tooth movement and all these parameters altered by the applied treatment.

Conclusions: OPG-Fc effectively inhibits osteoclastogenesis resulting in improved bone quantity and orthodontic anchorage. Based on present results, OPG-Fc could have clinical utility in preventing undesired tooth movements.

MeSH terms

  • Animals
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical / methods
  • Male
  • Maxilla
  • Molar / drug effects
  • Molar / metabolism
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects
  • Osteoprotegerin / administration & dosage
  • Osteoprotegerin / pharmacology*
  • Periodontal Ligament / drug effects
  • RANK Ligand / metabolism
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacology
  • Tooth Mobility / physiopathology
  • Tooth Mobility / prevention & control*
  • Tooth Movement Techniques / methods*

Substances

  • Osteoprotegerin
  • RANK Ligand
  • Recombinant Fusion Proteins