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ABSTRACT: Abstract Objective: To elucidate the effect of bone morphometric changes on orthodontic tooth movement (OTM) in zoledronic acid-treated ovariectomized rats. Materials and Methods: Twenty-one 10-week-old female Wistar rats were divided into ovariectomy (OVX), OVX with zoledronic acid administration (OVX + ZOL), and sham operation (control) groups. Two weeks after OVX, ZOL administration was initiated. Twelve weeks after OVX, a nickel-titanium closed-coil spring of 25-g force was applied mesially to the maxillary left first molar. In vivo micro-computed tomography (CT) of the left proximal tibia was performed for bone morphometric analysis every 2 weeks after OVX. In addition, OTM was investigated using micro-CT at 0, 12, and 14 weeks after OVX. Results: There were significant differences in the bone mineral content (BMC), bone volume (BV), BMC to tissue volume ratio (BMC/TV), and BV to TV ratio of trabecular bone between the control and OVX groups and also between the OVX + ZOL and OVX groups. In the OVX + ZOL group, increased BMC and BV in the cortical bone and increased bone mineral density (BMD) in the trabecular bone were observed. Interestingly, OTM in the OVX group was almost two times more than that in the control and OVX + ZOL groups. Moreover, OTM was correlated with BMD, BMC, BV, and BMC/TV in the trabecular bone. Conclusions: OVX accelerated OTM, while ZOL suppressed it. OTM demonstrated a significant negative relationship with trabecular bone mass.
The Angle Orthodontist 02/2013; · 1.21 Impact Factor
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ABSTRACT: Abstract Objective: To verify the hypothesis that appropriate acquisition of masticatory function and normal growth of the mandible are modified by malocclusion. Materials and Methods: Eighteen Jcl∶ICR mice were divided into two groups. In one group we shifted the mandible laterally using an occlusal guidance appliance, creating a posterior crossbite at 5 weeks of age. The other group served as control. After 10 weeks, three-dimensional jaw movements and muscle activities were recorded simultaneously during mastication. Microcomputed tomography scans were obtained in vivo to evaluate morphometric changes in the mandible. Results: (1) The jaw movement pattern in the sagittal plane showed significantly less anteroposterior excursion in the malocclusion group during the late-closing phase (power phase). (2) Electromyography showed significantly less masseter activity in the malocclusion group. (3) The condylar width and mandibular bone mineral density (BMD) were significantly reduced in the malocclusion mice compared to the normal mice. Conclusions: These findings suggest that optimization of the chewing pattern and acquisition of appropriate masticatory function is impeded by malocclusion. Altered mechanical loading to the mandible may cause significant reduction of condylar width and mandibular BMD.
The Angle Orthodontist 01/2013; · 1.21 Impact Factor
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ABSTRACT: A newly designed removable appliance with a shape-memory wire was used for the orthodontic treatment of the anterior teeth in an 11-year-old child who had autism and intellectual disability. The device was designed to reduce the lateral incisor crossbite and the central incisors' labial rotation. The child was treated for 1 year with this removable appliance. Tooth movement was analyzed using cephalograms and surface data were derived from study models. This device proved to be very durable. The lateral incisor crossbite was corrected, and the inclination of the upper central incisors and the interincisal angle were improved. This appliance exerts light and continuous orthodontic force, without requiring any adjustments of the spring wire. The appliance also facilitated orthodontic treatment in a child with intellectual disability in whom treatment with a standard orthodontic device would be unsuitable.
Special Care in Dentistry 01/2013; 33(1):35-9.
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ABSTRACT: The aim of this study was to investigate the effects of interferon (IFN)-γ on experimental tooth movement in mice using a murine experimental tooth movement model. An Ni-Ti closed-coil spring was inserted between the upper-anterior alveolar bones and the upper-left first molars in mice. We evaluated the relationship between local Ifn-γ mRNA levels and orthodontic tooth movement. In other experiments, IFN-γ was injected adjacent to each first molar every other day during tooth movement. After 12 days, the amount of tooth movement was measured. Tartrate-resistant acid phosphatase (TRAP)-positive cells at the pressure side of each experimental tooth were counted as osteoclasts. Local Ifn-γ mRNA expression increased with orthodontic tooth movement. The number of TRAP-positive cells increased on the pressure side of the first molar. In contrast, the degree of tooth movement and the number of TRAP-positive cells on the pressure side in IFN-γ-injected mice were less than those of control mice. IFN-γ was induced in experimental tooth movement, and could inhibit mechanical force-loaded osteoclastogenesis and tooth movement. These results suggest that IFN-γ might be useful in controlling orthodontic tooth movement because of its inhibitory action on excessive osteoclastogenesis during this movement.
Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 09/2012; 32(9):426-31. · 1.63 Impact Factor
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ABSTRACT: The effect of zoledronic acid, a potent and novel bisphosphonate, on tooth movement and orthodontically induced root resorption in osteoporotic animals systemically treated with zoledronic acid as similarly used in postmenopausal patients has not been elucidated. Therefore, this study was undertaken.
Fifteen 10-week-old female Wistar rats were divided into 3 groups: ovariectomy, ovariectomy + zoledronic acid, and control. Only the ovariectomy and ovariectomy + zoledronic acid groups underwent ovariectomies. Two weeks after the ovariectomy, zoledronic acid was administered only to the ovariectomy + zoledronic acid group. Four weeks after the ovariectomy, 25-g nickel-titanium closed-coil springs were applied to observe tooth movement and orthodontically induced root resorption.
There were significant differences in the amounts of tooth movement and orthodontically induced root resorption between the ovariectomy and the control groups, and also between the ovariectomy and the ovariectomy + zoledronic acid groups. There was no statistically significant difference in tooth movement and orthodontically induced root resorption between the ovariectomy + zoledronic acid and the control groups. Zoledronic acid inhibited significantly more tooth movement and significantly reduced the severity of orthodontically induced root resorption in the ovariectomized rats. The ovariectomy + zoledronic acid group showed almost the same results as did the control group in both tooth movement and orthodontically induced root resorption.
Zoledronic acid inhibits excessive orthodontic tooth movement and also reduces the risk of severe orthodontically induced root resorption in ovariectomized rats.
American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 05/2012; 141(5):563-73. · 1.33 Impact Factor
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ABSTRACT: The aim of this study was to examine the effect of chewing efforts on sensory and pain thresholds of the orofacial skin of symptom-free subjects. Fourteen healthy volunteers were recruited. Using a stair-case method, the tactile detection threshold (TDT) and the filament-prick pain detection threshold (FPT) on the cheek skin (CS) and the skin overlying the palm side of the thenar skin (TS) were measured before and after chewing gum for 5 min (Time 1: T1) and keeping the jaw relaxed for 5 min (Time 2: T2) as a control. Both for the test and control situation, the TDT was higher in all measurement sites after 5 min. As for the FPT, the reactions between T1 and T2 were quite opposite: the FPT increased and/or remained stable in T1, while, it decreased at all sites in T2. There were significant session effects (T1-T2) on the FPT at the left CS (P<0.01), right CS (P<0.05) and TS (P<0.05). The increase of TDT after chewing/no chewing could be due to habituation, while the decrease of FPT observed in the control situation might be due to sensitization, respectively. This potential sensitization, however, was not observed after chewing efforts. Further studies are needed to clarify the modulating effect of masticatory function on the trigeminal sensory system.
Archives of oral biology 03/2012; 57(9):1251-5. · 1.65 Impact Factor
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ABSTRACT: The aim of this study was to clarify the effect of the play between the bracket and the archwire on anterior tooth movement subjected to the retraction force from various lengths of power arms in sliding mechanics.
A three-dimensional finite element method was used to simulate en masse anterior tooth retraction in sliding mechanics. The displacements of the maxillary incisor and the archwire deformation were calculated when the retraction force was applied.
When a play did not exist, bodily movement was obtained at 5.0 mm length of power arm. In case a play existed, bodily movement was observed at the power arm length of 11.0 mm.
In the actual clinical situation, a bracket/archwire play and the torsion of the archwire within the bracket slot should be taken into consideration to prescribe an optimal power arm length and to achieve effective anterior tooth movement.
Journal of dental biomechanics. 01/2012; 3:1758736012461269.
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ABSTRACT: Interleukin (IL)-12 is an important cytokine for innate and adaptive immunity. We previously reported that IL-12 inhibits tumour necrosis factor (TNF)-α-mediated osteoclast formation by inducing apoptosis. We also reported that TNF-α plays an important role in mechanical loading-induced osteoclast formation and bone resorption during orthodontic tooth movement. In this study, we investigated the effects of IL-12 on mechanical tooth movement in mice.
A Ni-Ti closed coil spring was inserted between the upper incisors and the upper left first molar in mice. IL-12 was injected locally adjacent to the first molar every other day during the experimental period, at doses varying from 0 to 1.5μg/day. After 12 days, the animals were killed and their jaws were processed for histological evaluation using tartrate-resistant acid phosphatase (TRAP) and TdT-mediated dUTP-biotin nick end-labelling (TUNEL) staining, and measurements of the root resorption area.
In the IL-12-treated mice, tooth movement and root resorption appeared to be reduced. In TUNEL-stained sections, many apoptotic cells were recognized on the pressure side in the IL-12-treated mice.
Our findings suggest that IL-12 inhibits not only mechanical tooth movement, but also root resorption during orthodontic tooth movement. These findings may arise through apoptosis induced by IL-12.
Archives of oral biology 08/2011; 57(1):36-43. · 1.65 Impact Factor
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ABSTRACT: TNF-α has been recognized as an important factor for osteoclastogenesis and plays an important role in bone resorption under pathological conditions. IL-12 and IL-18, which are T-cell mediators, are also important inflammatory cytokines. We have reported that IL-12 and IL-18 induce apoptosis in bone marrow cells treated with TNF-α in vitro and that osteoclastogenesis is inhibited by the interaction of TNF-α-induced Fas and the IL-12-induced Fas ligand (FasL). However, the anti-FasL antibody could not completely inhibit apoptosis. Therefore, it is possible that IL-12 and IL-18 may also trigger some other apoptotic mechanisms. Nitric oxide (NO) may act as a mediator of the apoptotic effect. In this study, we examined whether NO causes the IL-12- and IL-18-induced apoptosis of bone marrow cells in TNF-α-mediated osteoclast formation. We found that NO production was induced in bone marrow cells cultured with IL-12 and IL-18 in the presence of TNF-α. When bone marrow cells were cultured with TNF-α, osteoclasts were formed. In contrast, when bone marrow cells were cultured with both TNF-α and IL-12 or IL-18, the adherent cells were induced to undergo apoptosis. Apoptosis was partially inhibited when bone marrow cells were treated with NO synthase inhibitors. Furthermore, IL-12 and IL-18 synergistically induced cell death and upregulated NO production in the presence of TNF-α. These results indicate that the simultaneous effects of TNF-α and IL-12 or IL-18 on bone marrow cells induce apoptosis and that apoptosis is induced by the production of NO.
Calcified Tissue International 07/2011; 89(1):65-73. · 2.38 Impact Factor
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ABSTRACT: To quantify the amount of tooth movement and orthodontically induced root resorption (OIRR) in ovariectomized rats.
Five 10-week-old female Wistar rats undergoing ovariectomy (OVX) were investigated as the experimental group, and the other five without ovariectomy served as the control group. Four weeks after ovariectomy, 25-g nickel-titanium closed-coil springs were applied mesially to the maxillary left first molars. Micro-computed tomography was taken at day 0, 1, 3, 7, 14, 21, and 28. At day 28, the molars were extracted. The surface area of root resorption craters, depth, and volume were measured using electron and laser scanning microscopes.
Tooth movement gradually increased with time throughout 28 days. There was a significant difference in the amount of tooth movement between the control group and the OVX group. For OIRR, the OVX group showed wide and shallow root resorption craters scattered on the mesial root. The deep resorption craters were observed on the distal roots distributed in the cervical, middle, and apical thirds of the roots. Statistically significant differences were found between the control and the OVX groups in the depth and the volume of root resorption craters in the distal roots and the total volume of root resorption craters in all three roots.
Ovariectomy affected not only tooth movement but also OIRR. Tooth movement in the OVX group was more rapid than the control group. Furthermore, the amount of OIRR in the OVX group was more severe than the control group.
The Angle Orthodontist 03/2011; 81(4):570-7. · 1.21 Impact Factor
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ABSTRACT: Even though the beneficial effects of fluoride on enamel and root caries have been well documented, limited data are available concerning the effect of fluoride on orthodontically induced root resorption and tooth movement. Our objective was to investigate the effect of systemic fluoride administered from birth to 12 weeks on orthodontically induced root resorption and tooth movement in rat molars.
Fifty male Wistar rats were randomly divided into 5 groups. The negative control group received no sodium fluoride and had no tooth movement. The positive control group received no sodium fluoride but had tooth movement. Three experimental groups received sodium fluoride at 45 ppm from birth to 2, 4, and 12 weeks, respectively. At week 10, a 50-g nickel-titanium coil spring was applied to the maxillary left first molar for 2 weeks. The rats were killed at 12 weeks of age. Movement of the maxillary first molars was measured in relation to the maxillary second molar on digitized cephalometric radiographs. Mesial and distal roots were examined by using scanning electron and 3-dimensional laser microscopes.
Fluoride reduced the depth, volume, and roughness of the resorption craters in the experimental groups. However, the area was similar to that in the positive control group. Regarding the duration of fluoride intake, the longer fluoride was administered via drinking water, the smaller the amount of tooth movement observed.
Fluoride in drinking water from birth reduced the severity of orthodontically induced root resorption, but the amount of tooth movement was also decreased.
American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 02/2011; 139(2):196-205. · 1.33 Impact Factor
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ABSTRACT: Cytokines secreted by T cells play a pivotal role in inflammatory bone destruction. Tumor necrosis factor-α (TNF-α) is a major proinflammatory cytokine produced by macrophages following T cell activation, and directly promotes osteoclast differentiation resulting in accelerated bone resorption. Interferon-γ (IFN-γ) attenuates RANKL-initiated cellular signals through osteoclast formation and counterbalances aberrant bone resorption. With respect to this crosstalk during osteoclastogenesis, the direct interruption of IFN-γ in TNF-α-induced osteoclast formation still requires elucidation. We have demonstrated that IFN-γ directly inhibits osteoclastogenesis induced by TNF-α stimulation and accelerates apoptosis mediated by Fas/Fas ligand signals. There were a decreased number of osteoclasts and reduced mRNA levels encoding Nfatc1 in cultured bone marrow macrophages. Apoptotic responses of cultured cells were observed, with accelerated nuclear fragmentation in osteoclast precursor cells and increased FasL mRNA levels in bone marrow cells stimulated with TNF-α evident. IFN-γ reduced the level of osteoclastogenesis in response to TNF-α treatment in vivo. IFN-γ inhibited TNF-α-induced osteoclastogenesis in mice with T cells that had been exposed to anti-CD4 and -CD8 antibodies. These results provide evidence that IFN-γ directly inhibits osteoclastogenesis and induces cells apoptosis by Fas/FasL signals, leading to the indirect regulation of bone resorption, which is required for protective roles in bone destruction at an inflammation site.
Immunology letters 02/2011; 137(1-2):53-61. · 2.91 Impact Factor
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ABSTRACT: Root resorption is a side effect of orthodontic treatment that occurs with the removal of hyalinized tissue. Studies have shown that a reparative process in the periodontium begins when the applied orthodontic force is discontinued or reduced below a certain level. However, quantitative 3-dimensional evaluation of root resorption repair has not been done. The aim of this study was to quantitatively assess the 2- and 3-dimensional changes of root resorption craters after 2 weeks of continuous mesially applied orthodontic forces of 50 g on rat molars and 2- to 16-week retention periods.
We used 60 male Wistar rats (10 weeks old). Nickel-titanium closed-coil springs were used to apply 50-g mesial forces for 2 weeks to move the maxillary left first molars. The rats were randomly allocated to 6 groups. Those in the zero-week retention group were killed after force application. In the remaining 5 groups, the interdental spaces between the maxillary first and second molars were filled with resin to retain the molars. The molars were extracted after periods of retention from 2 and 16 weeks. The maxillary right molars were used as the controls. Mesial and distal roots (distobuccal and distopalatal) were examined by using scanning electron and 3-dimensional scanning laser microscopes. The surface area, depth, volume, and roughness of the root resorption craters were measured.
The area, depth, and volume of the craters decreased gradually and showed similar trends over the retention time, approaching a plateau at the 12th week. After 16 weeks of retention, the volumes of the resorption craters of the distobuccal and distopalatal roots reached recovery peaks of 69.5% and 66.7%, respectively. Small pits on the mesial roots showed recovery of 62.5% at the 12th week. The healing patterns in distal roots with severe resorption and mesial roots with shallow resorption had no significant differences.
The resorption and repair processes during the early stages of retention are balanced, and most of the reparative process occurs after 4 weeks of passive retention after the application of orthodontic force. Frequent orthodontic reactivations should be avoided to allow recovery and repair of root surface damage.
American journal of orthodontics and dentofacial orthopedics: official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 04/2010; 137(4):477-85. · 1.33 Impact Factor
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ABSTRACT: It has recently been reported that tumor necrosis factor (TNF)-alpha has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine interleukin (IL)-18 inhibits TNF-alpha-mediated osteoclastogenesis in mouse bone marrow cultures. In the present study, the effect of IL-18 on TNF-alpha-mediated osteoclastogenesis was investigated in vivo. We administered TNF-alpha with or without IL-18 into the supracalvaria of mice. The number of osteoclasts in the suture of the calvaria was increased in mice administered TNF-alpha. The number of osteoclasts in mice administered both TNF-alpha and IL-18 was lower than that in mice administered TNF-alpha alone. We previously showed that IL-12 and IL-18 synergistically inhibit TNF-alpha-mediated osteoclastogenesis in vitro. To assess the ability of these two cytokines to synergistically inhibit TNF-alpha-induced osteoclastogenesis in vivo, mice were administered the two cytokines at doses that did not inhibit osteoclast formation. The combination of IL-12 and IL-18 markedly inhibited TNF-alpha-induced osteoclastogenesis in vivo. To evaluate how IL-12 and IL-18 synergistically affect TNF-alpha-induced osteoclastogenesis, the IL-18 receptor (IL-18R) and IL-12R expression levels were analyzed by RT-PCR in bone marrow cells cultured with IL-12 or IL-18. IL-18R mRNA was increased in cells cultured with IL-12, while IL-12R mRNA was increased in cells cultured with IL-18. In addition, IL-18 inhibited TNF-alpha-induced osteoclastogenesis in mice with T-cell depletion caused by anti-CD4 and anti-CD8 antibodies. The present results suggest that IL-18 may inhibit TNF-alpha-mediated osteoclastogenesis in vivo via a T cell-independent mechanism.
Calcified Tissue International 03/2010; 86(3):242-8. · 2.38 Impact Factor
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ABSTRACT: To determine optimal loading conditions such as height of retraction force on the power arm and its position on the archwire in sliding mechanics.
A 3D finite element method (FEM) was used to simulate en masse anterior teeth retraction in sliding mechanics. The degree of labiolingual tipping of the maxillary central incisor was calculated when the retraction force was applied to different heights of a power arm set mesial or distal to the canine.
When the power arm was placed mesial to the canine, at the level of 0 mm (bracket slot level), uncontrolled lingual crown tipping of the incisor was observed and the anterior segment of the archwire was deformed downward. At a power arm height of 5.5 mm, bodily movement was produced and the archwire was less deformed. When the power arm height exceeded 5.5 mm, the anterior segment of the archwire was raised upward and lingual root tipping occurred. When the power arm was placed distal to the canine, lingual crown tipping was observed up to a level of 11.2 mm.
Placement of the power arm of an archwire between the lateral incisor and canine enables orthodontists to maintain better control of the anterior teeth in sliding mechanics. Both the biomechanical principles associated with the tooth's center of resistance and the deformation of the archwire should be taken into consideration for predicting and planning orthodontic tooth movement.
The Angle Orthodontist 11/2009; 79(6):1102-7. · 1.21 Impact Factor
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ABSTRACT: To test the efficacy of an animal model of pain and stress and evaluate the effects of celecoxib administered when orthodontic force is applied.
A 20-g reciprocal force was applied via an orthodontic appliance to the maxillary left first and second molars of 7-week-old male Sprague-Dawley rats. Rat behavior was evaluated at 5, 24, and 48 hours after the appliance was set. Behavior was assessed in a test field by the number of lines crossed in the first 30 seconds and 5 minutes following force application; number of lines crossed to the center; rearing time; and facial grooming time. Experimental group 1 received intraperitoneal administration of 30 mg/kg celecoxib before every behavioral test. Experimental group 2 received 90 mg/kg before the first behavioral test, and physiologic saline was administered before the remaining behavioral tests. Control groups received saline before every behavioral test and were given passive (passive control group) and active (active control group) appliances, respectively.
Parameters related to pain increased in the active controls, whereas the parameters in the experimental groups decreased to the level seen in the passive controls. Statistically significant differences in pain-related behavior between control and experimental groups were found at 5 and 24 hours after placing the appliance. Stress-related behavior was significantly less in the experimental groups compared to the active control group during experimental periods.
The administration of celecoxib relieves pain- and stress-related behavior evoked by orthodontic tooth movement in the rat. This model might be a useful tool for the evaluation of pain and stress.
The Angle Orthodontist 11/2009; 79(6):1169-74. · 1.21 Impact Factor
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ABSTRACT: Mechanical stress such as orthodontic tooth movement induces osteoclastogenesis. Sometimes, excessive mechanical stress results in root resorption during orthodontic tooth movement. It has been reported that bisphosphonate inhibits osteoclastogenesis. Recently, there have been concerns for orthodontic patients receiving bisphosphonates. Thus, the aim of this study was to investigate the effect of bisphosphonates on orthodontic tooth movement and root resorption in mice. A nickel-titanium (Ni-Ti) closed coil spring delivering a force of 10 g was inserted between the upper anterior alveolar bone and the first molar in 8-week-old male C57BL/6 mice. Bisphosphonate (2 microg/20 microl) was injected daily into a local site adjacent to the upper molar. After 12 days, the distance the tooth had moved was measured. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was counted as osteoclasts in histological sections. Root resorption was assessed by scanning electron microscopy. The data were analysed with a Student's t-test. The orthodontic appliance increased the number of osteoclasts on the pressure side and mesial movement of the first molar. Bisphosphonates reduced the amount of tooth movement and the number of osteoclasts. In addition, they also reduced root resorption on the pressure side. Bisphosphonates inhibit orthodontic tooth movement and prevent root resorption during orthodontic tooth movement in mice. These results suggest that bisphosphonates might have an inhibiting effect on root resorption during orthodontic tooth movement in humans and that they may interrupt tooth movement in orthodontic patients undergoing treatment, thus altering the outcome of treatment.
The European Journal of Orthodontics 10/2009; 31(6):572-7. · 0.89 Impact Factor
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ABSTRACT: To examine the effect of anti-c-Fms antibody on odontoclastogenesis and root resorption in an orthodontic tooth movement mouse model.
We used orthodontic tooth movement in which an Ni-Ti coil spring was inserted between the upper incisors and the upper first molar. Root resorption occurred in this model. Anti-c-Fms antibody was injected daily into a local site for 12 days during mechanical loading. Odontoclastogenesis and root resorption were assessed by histology and scanning electron microscopy.
The anti-c-Fms antibody significantly inhibited odontoclastogenesis and root resorption during orthodontic tooth movement.
M-CSF and/or its receptor is a potential therapeutic target in mechanical stress- induced odontoclastogenesis, and injection of an anti-c-Fms antibody might be useful for inhibition of mechanical stress-induced root resorption during orthodontic tooth movement.
The Angle Orthodontist 10/2009; 79(5):835-41. · 1.21 Impact Factor
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ABSTRACT: It has been reported that TNF-alpha plays an important role in bone resorption in pathological conditions. IL-12, which is a T cell mediator, is also an important inflammatory cytokine. We previously reported that IL-12 induces apoptosis in bone marrow cells treated with TNF-alpha in vitro via an interaction between TNF-alpha-induced Fas and IL-12-induced Fas ligand (FasL), and that, as a result, osteoclastogenesis is inhibited. The purpose of this study was to investigate the effects of IL-12 on TNF-alpha-mediated osteoclastogenesis in vivo. We administered TNF-alpha with and without IL-12 into the supracalvaria in mice. The numbers of osteoclasts in the sutures in the calvaria were higher in mice administered TNF-alpha than in control mice not administered TNF-alpha. The numbers of osteoclasts in mice administered both TNF-alpha and IL-12 were lower than those in mice administered only TNF-alpha. Next, we determined the levels of mRNAs for cathepsin K and tartrate-resistant acid phosphatase (TRAP). mRNA levels were increased in mice administered TNF-alpha compared with control mice, but not in mice administered both TNF-alpha and IL-12. We also evaluated the amounts of tartrate-resistant acid phosphatase 5b (TRACP 5b) in mouse sera. The levels of TRACP 5b in mice administered TNF-alpha were higher than those in control mice. On the other hand, in mice administered both TNF-alpha and IL-12, the levels were lower than those in mice administered TNF-alpha alone. Fas and FasL expression levels were analyzed by real-time RT-PCR. The levels of Fas mRNA were increased in the calvaria of mice administered TNF-alpha compared with control mice, while those of FasL mRNAs were increased in the calvaria of mice administered IL-12. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, many apoptotic cells were found in the sutures in the calvaria of mice administered both TNF-alpha and IL-12. IL-12 also inhibited TNF-alpha-induced osteoclastogenesis in mice whose T cells were blocked by anti-CD4 and anti-CD8 antibodies. These results suggest that IL-12 inhibits TNF-alpha-mediated osteoclastogenesis and induces apoptotic changes through an interaction between TNF-alpha-induced Fas and IL-12-induced FasL, in vivo, via a T cell-independent mechanism.
Bone 08/2009; 45(5):1010-6. · 4.02 Impact Factor
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ABSTRACT: To test the hypothesis that the administration of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone have no effect on root resorption and tooth movement.
A mesial force of 50 g was applied to the left maxillary first molars of sixty 10-week-old male Wistar rats using nickel titanium closed coil springs attached to the cervical area of the incisors. The rats were randomly divided into 12 groups of 5 each. High and low doses of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone were administered via drinking water for 2 weeks. The experimental control group had tooth movement but received no drug. The negative control group received neither tooth movement nor drugs. The amount of tooth movement was measured on digitized lateral cephalometric radiographs. Rats were sacrificed after 2 weeks. Mesial and distal roots (distobuccal and distopalatal) were examined using scanning electron and three-dimensional (3D) scanning laser microscopes. The surface area, depth, volume, and roughness of the root resorption craters were measured.
When compared with experimental control rats, only prednisolone- and high-dose celecoxib-treated groups showed significantly less root resorption and less tooth movement. Although low dose celecoxib-treated group significantly decreased the tooth movement, root resorption was similar to the control group. Furthermore, resorption craters showed a smoother surface in the prednisolone-treated rats.
The hypothesis was rejected. Administration of prednisolone and high-dose celecoxib reduces root resorption and interferes with tooth movement in rats. Both drugs may interfere in the arachidonic acid cascade depending on dose thresholds.
The Angle Orthodontist 08/2009; 79(4):715-26. · 1.21 Impact Factor
