Assessment of the Role of NO-cGMP Pathway in Orthodontic Tooth Movement Using PDE5 Inhibitors: An Animal Study
Objectives: 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.
Materials and 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.
- Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene. 2006 Feb;367:1-16.
- Shirazi M, Nilforoushan D, Alghasi H, Dehpour AR. The role of nitric oxide in orthodontic tooth movement in rats. Angle Orthod. 2002 Jun;72(3):211-5.
- Hayashi K, Igarashi K, Miyoshi K, Shinoda H, Mitani H. Involvement of nitric oxide in orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop. 2002 Sep;122(3):306-9.
- Akin E, Gurton AU, Olmez H. Effects of nitric oxide in orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop. 2004 Nov;126(5): 608-14.
- Nilforoushan D, Manolson MF. Expression of nitric oxide synthases in orthodontic tooth movement. Angle Orthod. 2009 may;79(3):502-8.
- Ralston SH, Grabowski PS. Mechanisms of cytokine induced bone resorption: role of nitric oxide, cyclic guanosine monophosphate, and prostaglandins. Bone. 1996 Jul;19(1):29-33.
- Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop. 2006 Apr;129(4): 469.e1-32.
- Mancini L, Moradi-Bidhendi N, Becherini L, Martineti V, MacIntyre I. The biphasic effects of nitric oxide in primary rat osteoblasts are cGMP dependent. Biochem Biophys Res Commun. 2000 Aug;274(2):477-81.
- Damoulis PD, Hauschka PV. Cytokines induce nitric oxide production in mouse osteoblasts. Biochem Biophys Res Commun. 1994 Jun;201(2):924-31.
- Stanfeld J, Jones J, Laster L, Davidovitch Z. Biochemical aspects of orthodontic tooth movement. I. Cyclic nucleotide and prostaglandin concentrationsin tissues surrounding orthodontically treated teeth in vivo. Am J Orthod Dentofacial Orthop. 1986 Aug;90(2):139-48.
- Francis SH, Busch JL, Corbin JD, Sibley D. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010 Sep;62(3):525-63.
- Lin CS, Lin G, Xin ZC, Lue TF. Expression, distribution and regulation of phosphodiesterase 5. Curr Pharm Des. 2006;12(27):3439-57.
- Lin CS. Tissue expression, distribution, and regulation of PDE5. Int J Impot Res. 2004 Jun;16 Suppl 1:S8-S10.
- Gong Y, Xu CY, Wang JR, Hu XH, Hong D, Ji X, et al. Inhibition of phosphodiesterase 5 reduces bone mass by suppression of canonical Wnt signaling. Cell Death Dis. 2014 Nov;5:e1544.
- Yaman F, Atilgan S, Günes N, Agacayak S, Günay A, Ucan MC, et al. Phosphodiesterase-5 inhibitors may facilitate bone defect recovery. Eur Rev Med Pharmacol Sci. 2011 Nov;15(11):1301-5.
- Toque HA, Priviero FB, Teixeira CE, Claudino MA, Baracat JS, Fregonesi A, et al. Comparative relaxing effects of sildenafil, vardenafil, and tadalafil in human corpus cavernosum: contribution of endogenous nitric oxide release. Urology. 2009 Jul;74(1):216-21.
- Lau LC, Adaikan PG. Mechanisms of direct relaxant effect of sildenafil, tadalafil and vardenafil on corpus cavernosum. Eur J Pharmacol. 2006 Jul;541(3):184-90.
- Akhoundi MS, Dehpour AR, Rashidpour M, Alaeddini M, Kharazifard MJ, Noroozi H. The effect of morphine on orthodontic tooth movement in rats. Aust Orthod J. 2010 Nov;26(2):113-8.
- Rashidpour M, Ahmad Akhoundi MS, Nik TH, Dehpour A, Alaeddini M, Javadi E, et al. Effect of Tramadol (μ-opioid receptor agonist) on orthodontic tooth movements in a rat model. J Dent (Tehran). 2012 Spring;9(2):83-9.
- Mirhashemi AH, Afshari M, Alaeddini M, Etemad-Moghadam S, Dehpour A, Sheikhzade S, et al. Effect of atorvastatin on orthodontic tooth movement in male Wistar rats. J Dent (Tehran). 2013Nov;10(6):532-9.
- Mirhashemi AH, Ahmad Akhoundi MS, Sheikhzadeh S, Momeni N, Dehpour A, Alaeddini M, et al. Effect of fluoxetine consumption on orthodontic tooth movement in rats. J Dent (Tehran). 2015 Dec;12(12):882-9.
- Ahmad Akhoundi MS, Ghazanfari R, Etemad-Moghadam S, Alaeddini M, Khorshidian A, Rabbani S, et al. Effect of supplementary zinc on orthodontic tooth movement in a rat model. Dental Press J Orthod. 2016 Mar-Apr;21(2):45-50.
- Yaroslavskiy BB, Li Y, Ferguson DJ, Kalla SE, Oakley JI, Blair HC. Autocrine and paracrine nitric oxide regulate attachment of human osteoclasts. J Cell Biochem. 2004 Apr;91(5):962-72.
- Meikle MC. The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod. 2006 Jun;28(3):221-40.
- Kaji H, Sugimoto T, Kanatani M, Fukase M, Kumegawa M, Chihara K. Prostaglandin E2 stimulates osteoclast-like cell formation and bone-resorbing activity via osteoblasts: role of cAMP-dependent protein kinase. J Bone Miner Res. 1996 Jan;11(1):62-71.
- Ahlström M, Pekkinen M, Huttunen M, Lamberg-Allardt C. Cyclic nucleotide phosphodiesterases (PDEs) in human osteoblastic cells; the effect of PDE
inhibition on cAMP accumulation. Cell Mol Biol Lett. 2005;10(2):305-19.
- Takami M, Cho ES, Lee SY, Kamijo R, Yim M. Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: possible involvement of ERK and p38 MAPK pathways. FEBS Lett. 2005 Jan;579(3):832-8.
- Histing T, Marciniak K, Scheuer C, Garcia P, Holstein JH, Klein M, et al. Sildenafil accelerates fracture healing in mice. J Orthop Res. 2011 Jun;29(6):867-73.
- Di Domenico M, D'apuzzo F, Feola A, Cito L, Monsurrò A, Pierantoni GM, et al. Cytokines and VEGF induction in orthodontic movement in animal models. J Biomed Biotechnol. 2012;2012:201689.
- Bletsa A, Virtej A, Berggreen E. Vascular endothelial growth factors and receptors are up-regulated during development of apical periodontitis. J Endod. 2012 May;38(5):628-35.
- Nakagawa M, Kaneda T, Arakawa T, Morita S, Sato T, Yomada T, et al. Vascular endothelial growth factor (VEGF) directly enhances osteoclastic bone resorption and survival of mature osteoclasts. FEBS Lett. 2000 May;473(2):161-4.
- Vidavalur R, Penumathsa SV, Zhan L, Thirunavukkarasu M, Maulik N. Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor. Vascul Pharmacol. 2006 Aug;45(2):91-5.
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|Nitric Oxide Phosphodiesterase 5 Inhibitors Tooth Movement Techniques|
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