title: Assessment of the Role of NO-cGMP Pathway in Orthodontic Tooth Movement Using PDE5 Inhibitors: An Animal Study.
abstract: OBJECTIVE
  Nitric oxide (NO) is a signaling molecule that mediates mechanical bone loading. Cyclic guanosine 3', 5' monophosphate (cGMP) is a NO-induced effector molecule. The aim of this study was to assess the effect of NO-cGMP pathway on orthodontic tooth movement (OTM) in rats by use of two phosphodiesterase 5 (PDE5) inhibitors namely sildenafil and tadalafil as chemical tools.
  
  
  METHODS
  Forty-five male Wistar rats were divided into three equal groups (n=15) based on the substance they received. The first group received daily injections of tadalafil; the second group received daily injections of sildenafil and the third group received daily injections of normal saline. The orthodontic appliances consisted of nickel-titanium closed-coil spring ligated between the maxillary right incisor and the first molar of the animals for 21 days. The amount of tooth movement was measured in all three groups at the end of this period. Histological analysis was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) thickness.
  
  
  RESULTS
  All appliance-treated molars in the experimental and control groups showed evidence of tooth movement. The mean OTM was calculated to be 0.39±0.16, 0.32±0.16 and 0.26±0.16mm in tadalafil, sildenafil and control groups, respectively and there were no significant differences in OTM among the study groups (P>0.05). In the tadalafil group, significantly greater root resorption on the tension side was seen when compared with controls (P≤0.05).
  
  
  CONCLUSIONS
  Tadalafil and sildenafil PDE-5 inhibitors affecting the NO-cGMP pathway did not affect OTM in rats.
authors.affiliation: Associate Professor, Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Orthodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Mirhashemi
authors.affiliation: Professor, Laser Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Orthodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Sadegh Ahmad
authors.initials: MS
authors.lastname: Akhoundi
authors.affiliation: Assistant Professor, Department of Prosthodontics, School of Dentistry, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rezvaneh
authors.initials: R
authors.lastname: Ghazanfari
authors.affiliation: Associate Professor, Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahroo
authors.initials: S
authors.lastname: Etemad-Moghadam
authors.affiliation: Associate Professor, Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Alaeddini
authors.affiliation: PhD Candidate, Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Khorshidian
authors.affiliation: Professor, Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: PhD Candidate, Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Momeni
keywords: Nitric Oxide; Phosphodiesterase 5 Inhibitors; Tooth Movement Techniques