title: Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.
abstract: Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Christiaan M
authors.initials: CM
authors.lastname: Suttorp
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Ditte M S
authors.initials: DM
authors.lastname: Lundvig
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Kuijpers-Jagtman
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Jasper Tom
authors.initials: JT
authors.lastname: Uijttenboogaart
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Van Rheden
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Maltha
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud university medical centre, Radboud Institute for Molecular Life Sciences Nijmegen, Netherlands.
authors.forename: Frank A D T G
authors.initials: FA
authors.lastname: Wagener
keywords: alveolar bone remodeling; cytoprotective enzymes; hyalinization; orthodontic tooth movement; root resorption