HIF-2α Inhibits Ameloblast Differentiation via Hey2 in Tooth Development.

Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α-Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.

Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.

Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 µg/5 µL per joint), isotype control (rat IgG 10 µg/5 µL per joint) or PBS (5 µl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA.

Resin monomers act as adjuvants in Ni-induced allergic dermatitis in vivo.

Resin monomers (RMs) are inflammatory agents and are thought to cause allergic contact dermatitis (ACD). However, mouse models are lacking, possibly because of the weak antigenicities of RMs. We previously reported that inflammatory substances can promote the allergic dermatitis (AD) induced by intradermally injected nickel (Ni-AD) in mice. Here, we examined the effects of RMs on Ni-AD. To sensitize mice to Ni, a mixture containing non-toxic concentrations of NiCl2 and an RM [either methyl methacrylate (MMA) or 2-hydroxyethyl methacrylate (HEMA)] was injected intraperitoneally or into ear-pinnae intradermally. Ten days later, a mixture containing various concentrations of NiCl2 and/or an RM was intradermally injected into ear-pinnae, and ear-swelling was measured. In adoptive transfer experiments, spleen cells from sensitized mice were transferred intravenously into non-sensitized recipients, and 24 h later NiCl2 was challenged to ear-pinnae. Whether injected intraperitoneally or intradermally, RM plus NiCl2 mixtures were effective in sensitizing mice to Ni. AD-inducing Ni concentrations were greatly reduced in the presence of MMA or HEMA (at the sensitization step from 10 mM to 5 or 50 µM, respectively, and at the elicitation step from 10 µM to 10 or 100 nM, respectively). These effects of RMs were weaker in IL-1-knockout mice and in macrophage-depleted mice. Cell-transfer experiments in IL-1-knockout mice indicated that both the sensitization and elicitation steps depended on IL-1. Challenge with an RM alone did not induce allergic ear-swelling in mice given the same RM + NiCl2 10 days before the challenge. These results suggest that RMs act as adjuvants, not as antigens, to promote Ni-AD by reducing the AD-inducing concentration of Ni, and that IL-1 and macrophages are critically important for the adjuvant effects. We speculate that what were previously thought of as "RM-ACD" might include ACD caused by antigens other than RMs that have undergone promotion by the adjuvant effects of RMs.

An anti-c-Fms antibody inhibits osteoclastogenesis in a mouse periodontitis model.

OBJECTIVE: Bacterial lipopolysaccharide (LPS) can induce inflammatory bone loss such as periodontal disease. The formation of osteoclasts depends on macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kb ligand (RANKL). It has recently been reported that administration of an antibody of the M-CSF receptor c-Fms completely blocked osteoclastogenesis and bone erosion induced by LPS in mouse calvaria. In this study, the effect of antibody against c-Fms in the mouse periodontitis model by injection of LPS was investigated. MATERIALS AND METHODS: C57BL6/J mice were injected with LPS and anti-c-Fms antibody into the mesial gingiva of the first molar in the left mandible. Histological sections of periodontal tissue were stained for tartrate-resistant acid phosphatase, and osteoclast numbers and ratio of alveolar bone resorption determined. RESULTS: The number of osteoclasts and ratio of alveolar bone resorption in mice administered both LPS and anti-c-Fms antibody was lower than those in mice administered LPS alone. The expression of RANKL receptor, RANK, was inhibited by the anti-c-Fms antibody in periodontal tissue. CONCLUSION: M-CSF and/or its receptor are potential therapeutic targets for the treatment of bone resorption, caused by LPS, in periodontitis. Injection of an anti-c-Fms antibody might be useful for inhibition of pathological bone resorption in periodontitis.

Gap-junction-mediated communication in human periodontal ligament cells.

Periodontal tissue homeostasis depends on a complex cellular network that conveys cell-cell communication. Gap junctions (GJs), one of the intercellular communication systems, are found between adjacent human periodontal ligament (hPDL) cells; however, the functional GJ coupling between hPDL cells has not yet been elucidated. In this study, we investigated functional gap-junction-mediated intercellular communication in isolated primary hPDL cells. SEM images indicated that the cells were in contact with each other via dendritic processes, and also showed high anti-connexin43 (Cx43) immunoreactivity on these processes. Gap-junctional intercellular communication (GJIC) among hPDL cells was assessed by fluorescence recovery after a photobleaching (FRAP) analysis, which exhibited dye coupling between hPDL cells, and was remarkably down-regulated when the cells were treated with a GJ blocker. Additionally, we examined GJs under hypoxic stress. The fluorescence recovery and expression levels of Cx43 decreased time-dependently under the hypoxic condition. Exposure to GJ inhibitor or hypoxia increased RANKL expression, and decreased OPG expression. This study shows that GJIC is responsible for hPDL cells and that its activity is reduced under hypoxia. This is consistent with the possible role of hPDL cells in regulating the biochemical reactions in response to changes in the hypoxic environment.

Orthodontic miniscrew failure rate and root proximity, insertion angle, bone contact length, and bone density.

OBJECTIVES: To test the hypothesis that there is no significant correlation between miniscrew failure rate and root proximity, insertion angle, bone contact length, and bone density. SETTING AND SAMPLE POPULATION: This study included 107 patients in whom 190 miniscrews had been placed from April 2008 to October 2009 in Tohoku University Hospital (Sendai, Japan). MATERIALS AND METHODS: Cone beam computed tomography scans (CBCT) and periapical radiographs were taken before and after miniscrew placement. Differences in root proximity, screw insertion angle, bone contact length, and bone density were statistically compared; comparisons were also made between the CBCT images and periapical radiographs. RESULTS: A significantly higher success rate was observed in the maxilla than in the mandible. The distance between the miniscrew and the root surface was significantly smaller in the failure group. There were no significant differences in the insertion angle, bone contact length, or bone density between the success group and the failure group. The concordance rate between the periapical dental radiographs and CBCT images was 46.5%. CONCLUSION: While bone contact length, miniscrew angle, and bone density did not exert major effects on miniscrew failure, root proximity was the factor that most affected miniscrew failure, especially for miniscrews placed in the mandible. CBCT was superior to periapical dental X-rays for evaluating the proximity of miniscrews to the root. Correction of the X-ray attenuation coefficient value was necessary for measuring bone density using CBCT.

Cross-reactivity among some metals in a murine metal allergy model.

BACKGROUND: Information concerning cross-reactivity among metal allergens is scarce. We previously devised a murine metal allergy model using lipopolysaccharide (LPS) as an adjuvant. LPS reduces the minimum allergy-inducing concentration (MAIC) of metals at both the sensitization and the elicitation steps. OBJECTIVES: Here, we examined allergic cross-reactivity among some metals in this murine model, and compared the effects of ultrapure (99·99% or more) and low purity (93-99%) metal salts. METHODS: A mixture of a metal salt and Escherichia coli LPS was injected intraperitoneally into BALB/c mice (0·25 mL per mouse). Ten days later, metal salts (with or without LPS) were challenged to ear pinnas (20 µL per ear), and ear swelling was measured. RESULTS: Among the ultrapure metals tested (Ni, Pd, Co, Cr, Cu and Au), only Ni and Pd cross-reacted. In this cross-reaction, their MAICs were at the same level. Combined challenge with Ni and Pd at sub-MAICs (but not at higher concentrations) produced an additive effect. Surprisingly, mice sensitized with low purity Ni reacted to all the tested low purity metals (Ni, Pd, Co and Cr), and the low purity metals were shown to contain contaminant metals. CONCLUSIONS: In our model: (i) Ni and Pd (members of the same group in the periodic table of elements) cross-react with each other, (ii) this cross-reaction may depend on true and false antigens forming metal-protein complexes with similar spatial geometries, (iii) Co, Cr, Cu and Au do not cross-react with each other, (iv) in low purity materials, trace contaminant metals may be sufficient to evoke allergy, and thus (v) high purity metal salts should be considered for use in clinical patch testing.

Allergy-inducing nickel concentration is lowered by lipopolysaccharide at both the sensitization and elicitation steps in a murine model.

BACKGROUND: Nickel (Ni) is the major cause of contact allergy. We previously found that lipopolysaccharide (LPS, a cell-surface component of gram-negative bacteria) markedly promotes Ni allergy in a murine model. Establishing the minimum concentration or amount of Ni needed to induce allergic responses may help us to prevent or reduce such responses. OBJECTIVES: Using the above murine model, we examined the influence of LPS on the minimum allergy-inducing concentrations of Ni (Ni-MAICs) at the sensitization step and at the elicitation step. METHODS: BALB/c mice were sensitized by intraperitoneal injection of a mixture containing various concentrations of LPS and NiCl(2). Ten days later, their ear pinnas were challenged intradermally with a mixture containing various concentrations of LPS and NiCl(2), and ear swelling was measured. RESULTS: Without LPS, the Ni-MAICs at the sensitization and elicitation steps were around 1×10(-2) mol L(-1) and 1×10(-5) mol L(-1) , respectively. Sensitization with NiCl(2) + LPS did not alter the value at elicitation. Surprisingly, LPS markedly reduced these Ni-MAICs (to around 1×10(-6) molL(-1) at sensitization, with 25 µg mL(-1) LPS, and 1×10(-12) mol L(-1) at elicitation, with 0·5 µg mL(-1) LPS). The effect of LPS depended on its concentration and the timing of its injection. CONCLUSIONS: Our findings suggest that: (i) Ni-MAIC is higher at sensitization than at elicitation; (ii) once sensitization is established, Ni allergy can easily be induced by a low concentration of Ni; and (iii) a bacterial milieu or infection may greatly facilitate the establishment and elicitation of Ni allergy.

Effects of CO2 laser irradiation of the gingiva during tooth movement.

Patients often feel pain or discomfort in response to orthodontic force. It was hypothesized that CO(2) laser irradiation may reduce the early responses to nociceptive stimuli during tooth movement. The distribution of Fos-immunoreactive (Fos-IR) neurons in the medullary dorsal horn of rats was evaluated. Two hrs after tooth movement, Fos-IR neurons in the ipsilateral part of the medullary dorsal horn increased significantly. CO(2) laser irradiation to the gingiva just after tooth movement caused a significant decrease of Fos-IR neurons. PGP 9.5- and CGRP-positive nerve fibers were observed in the PDL of all study groups. The maximum temperature below the mucosa during CO(2) laser irradiation was less than 40 degrees C. It was suggested that CO(2) laser irradiation reduced the early responses to nociceptive stimuli during tooth movement and might not have adverse effects on periodontal tissue.

CTGF and apoptosis in mouse osteocytes induced by tooth movement.

It is known that experimental tooth movement stimulates the gene expression of connective tissue growth factor (CTGF) and induces apoptosis in osteocytes in rats. We hypothesized that there is a relationship between CTGF expression and the induction of apoptosis in osteocytes, to play a significant role in triggering bone remodeling during experimental tooth movement. In this study, CTGF mRNA expression was detected at 2 hours in osteocytes on the pressure side, followed by apoptosis at 6 hours after tooth movement in mice. The number of empty lacunae significantly increased on day 1 after mechanical stimulation. Thereafter, the number of osteoclasts significantly increased on the pressure side of the alveolar bone on day 3. Tooth movement increased rapidly on day 10. These findings suggest that CTGF expression, followed by apoptosis in osteocytes in response to mechanical stimulation, might play a significant role in triggering bone remodeling during tooth movement.

Increase of galanin in trigeminal ganglion during tooth movement.

It is known that nerve fibers containing neuropeptides such as galanin increase in the periodontal ligament during experimental tooth movement. However, the origin of galanin-containing nerve fibers in the periodontal ligament remains unclear. This study was conducted to examine our hypothesis that the increased galanin nerve fibers have a sensory neuronal origin, and that the peptide is associated with pain transmission and/or periodontal ligament remodeling during experimental tooth movement. In control rats, galanin-immunoreactive trigeminal ganglion cells were very rare and were observed predominantly in small ganglion cells. After 3 days of experimental tooth movement, galanin-immunoreactive trigeminal ganglion cells significantly increased, and the most marked increase was observed at 5 days after experimental tooth movement. Furthermore, their cell size spectrum also significantly changed after 3 and 5 days of movement: Medium-sized and large trigeminal ganglion cells began expressing, and continued to express, galanin until 14 days after experimental tooth movement. These findings suggest that the increase of galanin in the periodontal ligament during experimental tooth movement at least partially originates from trigeminal ganglion neurons and may play a role in pain transmission and/or periodontal remodeling.

Brain-derived neurotrophic factor-immunoreactive primary sensory neurons in the rat trigeminal ganglion and trigeminal sensory nuclei.

Immunohistochemistry for brain-derived neurotrophic factor (BDNF) was performed on the rat trigeminal ganglion (TG). The immunoreactivity (IR) was detected in 46% of TG neurons. These neurons were mostly small- or medium-sized (range, 149.7-1246.3 microm2; mean +/- SD = 373.4 +/- 151.6 microm2). A double immunofluorescence method also revealed that 54% of BDNF-immunoreactive (IR) neurons were immunoreactive for calcitonin-gene-related peptide. In addition, 93% of BDNF-IR TG neurons contained vanilloid receptor subtype 1. However, the co-expression of BDNF and vanilloid receptor 1-like receptor was very rare (less than 1%). In the trigeminal sensory nuclei, laminae II of the medullary dorsal horn was abundant in presumed BDNF-IR axon terminals. Such profiles were also detected in the dorsolateral part of the subnucleus oralis. The retrograde tracing and immunohistochemical methods demonstrated that BDNF-IR was common among cutaneous TG neurons (47%) but not tooth pulp TG neurons (13%). The present study indicates that BDNF-IR TG neurons have unmyelinated axons and project to the superficial medullary dorsal horn. It is likely that BDNF-containing neurons in both the trigeminal and spinal sensory systems have similarities in morphology and function. However, the content of BDNF in TG neurons probably depends on their peripheral targets. BDNF seems to convey nociceptive cutaneous input to the trigeminal sensory nuclei.

Occlusal force and condylar motion in patients with anterior open bite.

Patients with open bite often show a weak occlusal force and temporomandibular disorders (TMDs). If these are the main cause of open bite, it may be hypothesized that both pre-pubertal and adult open-bite patients would show a weak occlusal force and abnormal condylar motion. The purpose of this study was to test this hypothesis. Test group subjects consisted of 13 consecutive pre-pubertal and 13 adult patients with anterior open bite. They were compared with age-matched normal subjects. The adult open-bite group showed a weaker occlusal force and a shorter range of condylar motion compared with the control subjects. In the pre-pubertal subjects, however, there were no significant differences in the occlusal force and range of condylar motion between the open-bite and control groups. Therefore, these results suggest that a weak occlusal force or TMDs may not be the main cause of open bite.

Denervation resulting in dento-alveolar ankylosis associated with decreased Malassez epithelium.

Inferior alveolar nerve denervation causes appreciable decreases in the distribution of epithelial rests of Malassez. To explore roles of the Malassez epithelium, we attempted to evaluate possible changes in dento-alveolar tissues surrounding this epithelium by experimental denervation. We found that denervation led to dento-alveolar ankylosis with a decrease in the width of the periodontal spaces. Interestingly, with regeneration of the Malassez epithelium 10 weeks after the denervation, the periodontal space width showed a correspondingly significant increase. These findings suggest that the Malassez epithelium may be involved in the maintenance of periodontal space and that sensory innervation might be indirectly associated with it. In addition, it is of interest that denervation activated root resorption of the coronal root surface and that the consequently resorbed lacunae were repaired by cellular cementum. It is suggested that Malassez epithelium may negatively regulate root resorption and induce acellular cementum formation.

VR1-, VRL-1- and P2X3 receptor-immunoreactive innervation of the rat temporomandibular joint.

Immunohistochemistry for vanilloid receptor subtype 1 (VR1), vanilloid receptor 1-like receptor (VRL-1) and P2X3 receptor was performed in the rat temporomandibular joint (TMJ). Blood vessels in the articular disk and capsule, the synovial membrane and the fibrous tissue around the condylar process were innervated by VR1- or P2X3 receptor-immunoreactive (ir) nerve fibers. However, VRL-1-immunoreactivity (ir) could not be detected in the TMJ. Retrograde tracing and immunohistochemical methods revealed that 25%, 41% and 52% of TMJ neurons in the trigeminal ganglion (TG) exhibited VR1-, VRL-1- and P2X3 receptor-ir, respectively. VR1-ir TMJ neurons were mostly small to medium-sized, whereas VRL-1- and P2X3 receptor-ir TMJ neurons were predominantly medium-sized to large. In addition, 73%, 28% and 44% of VR1-, VRL-1- and P2X3 receptor-ir TMJ neurons, respectively, coexpressed calcitonin gene-related peptide (CGRP)-ir. The present study suggests that the TMJ has abundant nociceptors which respond to vanilloid compounds, protons, heat and extracellular ATP.

Galanin-immunoreactive nerve fibers in the periodontal ligament during experimental tooth movement.

Neuropeptides have been suggested to play a role in pain transmission during orthodontic tooth movement. We examined this hypothesis by examining the effect of orthodontic tooth movement on the expression of galanin (GAL)-immunoreactive (ir) nerve fibers in the periodontal ligament (PDL) of one mesial root (MR) and two distal roots (DRs) of the rat maxillary first molar. In control rats, GAL-ir fibers were very rare in the PDL. One day after the insertion of the elastic band, the number of GAL-ir fibers increased, becoming most numerous at 3 days. From 5 to 28 days, GAL-ir fibers tended to decrease. Electron microscopic observation showed that all of the GAL-ir fibers were unmyelinated. These findings suggest that GAL-containing nerve fibers in the PDL may play an important role in the response of the tissue to experimental tooth movement.

The use of small titanium screws for orthodontic anchorage.

The use of conventional dental implants for orthodontic anchorage is limited by their large size. The purpose of this study was to quantify the histomorphometric properties of the bone-implant interface to analyze the use of small titanium screws as an orthodontic anchorage and to establish an adequate healing period. Overall, successful rigid osseous fixation was achieved by 97% of the 96 implants placed in 8 dogs and 100% of the elastomeric chain-loaded implants. All of the loaded implants remained integrated. Mandibular implants had significantly higher bone-implant contact than maxillary implants. Within each arch, the significant histomorphometric indices noted for the "three-week unloaded" healing group were: increased labeling incidence, higher woven-to-lamellar-bone ratio, and increased osseous contact. Analysis of these data indicates that small titanium screws were able to function as rigid osseous anchorage against orthodontic load for 3 months with a minimal (under 3 weeks) healing period.

CTGF/Hcs24 induces chondrocyte differentiation through a p38 mitogen-activated protein kinase (p38MAPK), and proliferation through a p44/42 MAPK/extracellular-signal regulated kinase (ERK).

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24) promotes proliferation and differentiation of chondrocytes in culture. We investigated the roles of two major types of mitogen activated protein kinase (MAPK) in the promotion of proliferation and differentiation by CTGF/Hcs24. Here we report the effects of the MAPKK/MEK 1/2 inhibitor, PD098059, and p38 MAPK inhibitor, SB203580, in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) and rabbit growth cartilage (RGC) cells treated with CTGF/Hcs24. In the proliferation phase, CTGF/Hcs24 induced a approximately fivefold increase in the phosphorylation of p44/42 MAPK/ERK and a approximately twofold increase in that of p38 MAPK in an in vivo kinase assay. These inhibitors of MAPKK and MAPK suppressed phosphorylation of ets-like gene-1 (Elk-1) and nuclear activating transcription factor-2 (Atf-2) induced by CTGF/Hcs24 in a dose-dependent manner, respectively. Western blot analysis showed that phosphorylation of ERK was induced from 30 to 60 min and phosphorylation of p38 MAPK from 10 to 15 min after the addition of CTGF/Hcs24 in confluence HCS-2/8 cells. PD098059 suppressed the DNA synthesis of HCS-2/8 cells and RGC cells, while SB203580 did not. On the other hand, the p38 MAPK inhibitor, SB203580, completely inhibited the CTGF/Hcs24-induced synthesis of proteoglycans in HCS-2/8 cells and RGC cells but the MEK1/2 inhibitor, PD098059, did not. These results suggest that ERK mediates the CTGF/Hcs24-induced proliferation of chondrocytes, and that p38 MAPK mediates the CTGF/Hcs24-induced differentiation of chondrocytes.

Osteopontin-immunoreactivity in the rat trigeminal ganglion and trigeminal sensory nuclei.

Osteopontin-immunoreactivity (OPN-ir) was examined in the oro-facial tissues and trigeminal sensory nuclei (principal sensory nucleus and spinal trigeminal nucleus) to ascertain the peripheral ending and central projection of OPN-containing primary sensory neurons in the trigeminal ganglion (TG). No staining was observed using mouse monoclonal anti-OPN antibody preabsorbed with recombinant mature OPN. OPN-immunoreactive (ir) peripheral endings were classified into two types: encapsulated and unencapsulated types. Unencapsulated endings were subdivided into two types: simple and complex types. Simple endings were characterized by the thin neurite that was usually devoid of ramification. These endings were seen in the hard plate and gingiva. The complex type was characterized by the thick ramified neurite, and observed in the vibrissa, hard palate, and molar periodontal ligament. Encapsulated endings were found only in the hard palate. The trigeminal sensory nuclei contained OPN-ir cell bodies and neuropil. The neuropil was devoid of ir in laminae I and II of the medullary dorsal horn (MDH), and had various staining intensities in other regions of the trigeminal sensory nuclei. Transection of the infraorbital and inferior alveolar nerves caused an increase of OPN-ir intensity in ipsilateral TG neurons. The staining intensity of the neuropil also increased in the trigeminal sensory nuclei ipsilateral to the neurotomy excepting laminae I and II of the MDH. The present study indicates that OPN-ir primary sensory neurons in the TG innervate encapsulated and unencapsulated corpuscular endings. Such neurons probably project their central terminals to the trigeminal sensory nuclei except for the superficial laminae of the MDH.

Dentocraniofacial morphology of 12 Japanese subjects with unilateral cleft lip and palate with a severe Class III malocclusion: a cephalometric study at the pretreatment stage of surgical orthodontic treatment.

OBJECTIVE: The present study clarifies the dentocraniofacial morphology of patients with cleft lip and palate (CLP) with severe Class III malocclusion prior to surgical orthodontic treatment. METHODS: The sample was 12 Japanese male subjects with repaired complete unilateral CLP (surgical CLP group; 21.2 +/- 1.92 years in mean age). Two sets of patients without CLP Class III malocclusion, consisting of 19 male subjects treated by surgical orthodontic treatment (surgical Class III group; 23.4 +/- 6.35 years in mean age) and 14 male subjects treated by nonsurgical orthodontic treatment (nonsurgical Class III group; 18.7 +/- 3.49 years in mean age) were used as controls. Analyses were performed using lateral and posteroanterior (P-A) cephalograms. RESULTS: (1) The surgical CLP group showed significantly smaller values for overjet, SNA angle, and inclination of the maxillary incisor as compared with those of the surgical and nonsurgical Class III controls. The values of SNB, mandibular effective length, and ramus height in the surgical CLP group were significantly smaller than those of the surgical Class III group but were similar to those of the nonsurgical Class III group. (2) The mandible and the upper and lower dental arches deviated laterally toward the cleft side. The displacement of the mandible was correlated with that of the maxilla. These results show that CLP patients who required surgical orthodontic treatment had a characteristic dentocraniofacial morphology, compared to controls without CLP with Class III malocclusion.