Aya Maeda

Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation.

Osteoblasts express Toll like receptor (TLR) 4 and produce osteoclast-activating cytokines in response to the stimulation by lipopolysaccharide (LPS). It has recently been reported that LPS exerts an inhibitory effect on osteoblast differentiation into osteocytes. However, the molecular mechanisms of this inhibitory effect remain ambiguous. The downstream signals of TLR4 are mediated by adaptor molecules including myeloid differentiation factor 88 (MyD88), leading to the activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (ERKs), whose activation by LPS requires the upstream serine/threonine kinase, Cot/Tpl2. To determine the signal molecules responsible for the inhibitory effects of LPS on osteoblast differentiation, we examined the in vitro differentiation of the primary osteoblasts from myd88(-/-) and cot/tpl2(-/-) mice. The matrix mineralization by the wild-type and cot/tpl2(-/-) osteoblasts was significantly inhibited by LPS, whereas that of myd88(-/-) was not affected. During differentiation, LPS suppressed the mRNA expression of runt related transcription factor 2 (Runx2), osterix (Sp7), and activating transcription factor 4 (ATF4) in the wild-type, but not in the myd88(-/-) osteoblasts. The inhibitory effect of LPS on the mRNA expression of these transcription factors was absent in the early phase but partially impaired in the late phase of differentiation in the cot/tpl2(-/-) osteoblasts. Thus, the inhibitory effect of LPS on osteoblast differentiation is Myd88-dependent, whereas the degree of its requirement for Cot/Tpl2 varies depending on the differentiation phase.

Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1β, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1β abolished IL-8 induction by mechanical stresses, indicating that IL-1β is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.

Reduction of orthodontic tooth movement by experimentally induced periodontal inflammation in mice.

Orthodontic therapy is known to have an aggravating effect on the progression of destructive periodontitis if oral hygiene is not maintained. However, it is largely unknown how active periodontitis affects the velocity of orthodontic tooth movement. In this study, we examined the effect of periodontal inflammation on orthodontic tooth movement using a mouse model. Orthodontic force was applied on the maxillary first molar of mice, with or without ligature wire to induce experimental periodontitis. The distance moved by the first molar was significantly reduced by the ligature-induced experimental periodontitis. Tartrate-resistant acid phosphatase staining revealed that the number of osteoclasts present during orthodontic treatment was lower in the pressure zone of alveolar bone in the presence of periodontal inflammation. Consistently, the expression level of receptor activator of nuclear factor-kappaB ligand (RANKL) in the pressure zone was decreased in the ligature group. By contrast, experimental periodontitis increased the expression of cyclooxygenase-2 mRNA in the periodontal tissues, while in vitro treatment with prostaglandin E(2) decreased extracellular signal-regulated kinase phosphorylation and RANKL expression induced by mechanical stress in osteoblasts. Taken together, these results suggest that the orthodontic force-induced osteoclastogenesis in alveolar bone was inhibited by the accompanying periodontal inflammation, at least partly through prostaglandin E(2), resulting in reduced orthodontic tooth movement.

Orthodontic Treatment Combined with Mandibular Distraction Osteogenesis and Changes in Stomatognathic Function

We performed an orthodontic treatment combined with mandibular distraction osteogenesis in a 15-year-old patient who wanted a correction of a chin deficiency and a protruding upper lip. The patient had an Angle Class II division 1 malocclusion with mandibular retrusion, a low mandibular plane angle, and scissors bite. First, a quad-helix appliance was applied to the mandibular dentition to correct the scissors bite in the bilateral premolar region. Later, a preadjusted edgewise appliance was applied to the maxillary and mandibular teeth. After 3 days, a mandibular distraction osteogenesis was performed. During and after the distraction, the open bite between the upper and lower dental arches was corrected using up and down elastics. The total treatment time with the edgewise appliance was 14 months. A skeletal Class I apical base relationship, good facial profile, and optimum intercuspation of the teeth were achieved with the treatment. The jaw-movement pattern on the frontal view did not change during gum chewing. However, the maximum gap without pain increased. The electromyographic (EMG) activity of the masseter and anterior temporalis muscles, and maximum occlusal force increased. The present case report suggests that an orthodontic treatment combined with mandibular distraction osteogenesis in a patient with mandibular retrusion in the late growth period might be effective for improving stomatognathic function.

Induction of CXCL2 and CCL2 by pressure force requires IL-1β-MyD88 axis in osteoblasts.

Mechanical stresses including pressure force induce chemokine expressions in osteoblasts resulting in inflammatory reactions and bone remodeling. However, it has not been well elucidated how mechanical stresses induce inflammatory chemokine expressions in osteoblasts. IL-1β has been identified as an important pathogenic factor in bone loss diseases, such as inflammatory arthritis and periodontitis. Myeloid differentiation factor 88 (MyD88) is an essential downstream adaptor molecule of IL-1 receptor signaling. This study was to examine the gene expression profiles of inflammatory chemokines and the role of MyD88 in osteoblasts stimulated by pressure force. Pressure force (10g/cm(2)) induced significant mRNA increases of CXCL2, CCL2, and CCL5, as well as prompt phosphorylation of MAP kinases (ERK, p38 and JNK), in wild-type primary osteoblasts. The CXCL2 and CCL2 mRNA increases and MAP kinase phosphorylation were severely impaired in MyD88(-/-) osteoblasts. Constitutive low-level expression of IL-1β mRNA was similarly observed in both wild-type and MyD88(-/-) osteoblasts, which was not altered by pressure force stimulation. Notably, neutralization of IL-1β with a specific antibody significantly impaired pressure force-induced mRNA increases of CXCL2 and CCL2, as well as MAP kinase phosphorylation, in wild-type osteoblasts. Furthermore, pre-treatment with recombinant IL-1β significantly enhanced MAP kinase phosphorylation and mRNA increases of CXCL2 and CCL2 by pressure force in wild-type but not MyD88(-/-) osteoblasts. These results have suggested that the activation of MyD88 pathway by constitutive low-level IL-1β expression is essential for pressure force-induced CXCL2 and CCL2 expression in osteoblasts. Thus MyD88 signal in osteoblasts may be required for bone resorption by pressure force through chemokine induction.

Changes in Grafted Autogenous Bone During Edgewise Treatment in Patients With Unilateral Cleft Lip/Palate or Alveolus

Objective To examine the changes in autogenous bone from 6 to 12 months after alveolar bone grafting (ABG) (T1) through completion of edgewise treatment (T2). Design Retrospective longitudinal study. Setting Multidisciplinary long-term follow-up at Kagoshima University Hospital. Patients Forty-three patients with unilateral cleft lip and palate or alveolus. Main Outcome Measures At T1 and T2, the bone bridge and quantity of grafted bone were evaluated using the Chelsea scale and the ABG scale. The cleft-adjacent tooth angles before ABG and at T2, as well as the number of orthodontic space closures, were examined. Patients were classified as having either adequate (type A or C; adequate group) or poor bone bridges (type B, D, E, or F; poor group) by the assessment at T1. Results At T1, the ABG scores for the cleft-adjacent central incisor side of patients in the adequate group were higher than those of patients in the poor group (P < .001). At T2, the adequate group had higher ABG scores for the cleft-adjacent central incisor side (P = .022) and the canine sides (P = .034). No significant differences in tooth angles or the number of orthodontic space closures were noted between the groups. Conclusions These results suggest that the quantity of grafted bone in the cleft-adjacent central incisor at 6 to 12 months post-ABG may be an indicator of the quantity of grafted bone that will be present after edgewise treatment.

Outcome Following Secondary Autogenous Bone Grafting Before and After Canine Eruption in Patients With Unilateral Cleft Lip and Palate

Objective To determine whether the long axis and eruption of the cleft-adjacent canine affect postoperative outcomes in secondary autogenous bone grafting (SABG). Design Retrospective longitudinal study. Setting Multidisciplinary long-term follow-up at Kagoshima University Hospital. Subjects and Methods Twenty-five patients with complete unilateral cleft lip and palate (11 male, 14 female) were compared between unerupted and erupted groups for canine developmental stage, canine angle, and vertical height at bone grafting at 1 year and more than 4 years after SABG. The interalveolar septal heights at 1 and more than 4 years were evaluated by orthopantomograms. Results All patients in both groups accomplished dental rehabilitation with orthodontic treatment alone without prosthetic appliances. Although the rate of an acceptable bone bridge tended to be lower in the unerupted group (62.5%) than in the erupted group (88.8%), the difference was not significant (P = .158). The canine angle at bone grafting was significantly different between acceptable (69.2° ± 12.2°) and poor cases (77.3° ± 6.2°) at more than 4 years in the unerupted group (P = .049). The acceptable bone bridge rate might reflect mechanical stress added by natural eruption and orthodontic force. Conclusions We suggest that SABG should be planned in accordance with the canine angle, crown and root development, the eruption position of the cleft-adjacent canine, and the timing of added mechanical stress in the alveolar cleft, considering the bone formation in the alveolar cleft.

Relationships between the root-crown ratio and the loss of occlusal contact and high mandibular plane angle in patients with open bite

OBJECTIVE To determine the root-crown (R/C) ratio and dental root length of teeth in patients with open bite and seek any relationships with occlusal contact (OC) and the mandibular plane (Mp) angle. MATERIALS AND METHODS Thirty-one patients with open bite with negative overbite of at least four anterior teeth and 31 control patients with clinically normal overjet and overbite were enrolled. R/C ratios, dental root length, OC, and Mp angle were measured using panoramic radiographs, dental casts, and cephalograms, respectively. Mean differences between the groups, and variations between the R/C ratio or root length and Mp angle in patients with open bite were statistically analyzed. RESULTS R/C and OC ratios from the incisors to premolars were significantly lower for patients with open bite than for controls, and some teeth had short dental roots. Relationships between low R/C ratio or root length and high Mp angle were significant in patients with open bite. CONCLUSION Patients with open bite, especially those with a high Mp angle, have an unfavorable R/C ratio and short dental roots in some teeth, which may be related to the loss of OC.

Patient with oligodontia treated with a miniscrew for unilateral mesial movement of the maxillary molars and alignment of an impacted third molar

This report describes the treatment of a 20-year-old woman with a dental midline deviation and 7 congenitally missing premolars. She had retained a maxillary right deciduous canine and 4 deciduous second molars, and she had an impacted maxillary right third molar. The maxillary right deciduous second molar was extracted, and the space was nearly closed by mesial movement of the maxillary right molars using an edgewise appliance and a miniscrew for absolute anchorage. The miniscrew was removed, and the extraction space of the maxillary right deciduous canine was closed, correcting the dental midline deviation. After the mesial movement of the maxillary right molars, the impacted right third molar was aligned. To prevent root resorption, the retained left deciduous second molars were not aligned by the edgewise appliance. The occlusal contact area and the maximum occlusal force increased over the 2 years of retention. The miniscrew was useful for absolute anchorage for unilateral mesial movement of the maxillary molars and for the creation of eruption space and alignment of the impacted third molar in a patient with oligodontia.

Association of problem behavior with sleep problems and gastroesophageal reflux symptoms

There are few large‐scale epidemiologic studies examining the associations between sleep problems, gastroesophageal reflux disease (GERD) symptoms, lifestyle and food habits and problem behaviors (PB) in adolescents. The aim of this study was to evaluate the associations among these factors in Japanese adolescents.