title: Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement.
abstract: BACKGROUND
  The RANKL-OPG axis is a key regulator of osteoclastogenesis and bone turnover activity. Its contribution to bone resorption under altered mechanical states, however, has not been fully elucidated. Here we examined the role of OPG in regulating mechanically induced bone modeling in a rat model of orthodontic tooth movement.
  
  
  METHODS
  The maxillary first molars of male Sprague-Dawley rats were moved mesially using a calibrated nickel-titanium spring attached to the maxillary incisor teeth. Two different doses (0.5 mg/kg, 5.0 mg/kg) of a recombinant fusion protein (OPG-Fc), were injected twice weekly mesial to the first molars. Tooth movement was measured using stone casts that were scanned and magnified. Changes in bone quantity were measured using micro-computed tomography and histomorphometric analysis was used to quantify osteoclasts and volumetric parameters. Finally, circulating levels of TRAP-5b (a bone resorption marker) was measured using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The 5.0 mg/kg OPG-Fc dose showed a potent reduction in mesial molar movement and osteoclast numbers compared to controls (p<0.01). The molar movement was inhibited by 45.7%, 70.6%, and 78.7% compared to controls at days 7, 14, and 21 respectively, with the high dose of OPG. The 0.5 mg dose also significantly (p<0.05) inhibited molar movement at days 7 (43.8%) and 14 (31.8%). While incisor retraction was also decreased by OPG-Fc, the ratio of incisor to molar tooth movement was markedly better in the high-dose OPG group (5.2:1, p<0.001) compared to the control group (2.3:1) and the low-dose OPG group (2.0:1).
  
  
  CONCLUSIONS
  Local delivery of OPG-Fc inhibits osteoclastogenesis and tooth movement at targeted dental sites.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Dunn
authors.forename: Chan Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kostenuik
authors.forename: Sunil
authors.initials: S
authors.lastname: Kapila
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D014057:Tomography, X-Ray Computed; D014087:Tooth Movement Techniques
chemical_list: D007527:Isoenzymes; D053244:Osteoprotegerin; D011993:Recombinant Fusion Proteins; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase