Hydrogen peroxide-induced oxidative stress promotes expression of CXCL15/Lungkine mRNA in a MEK/ERK-dependent manner in fibroblast-like synoviocytes derived from mouse temporomandibular joint.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial disease caused by inflammation and oxidative stress. It has been hypothesized that mechanical stress-induced injury of TMJ tissues induces the generation of reactive oxygen species (ROS), such as hydroxyl radical (OH∙), in the synovial fluid (SF). In general, the overproduction of ROS contributes to synovial inflammation and dysfunction of the subchondral bone in OA. However, the mechanism by which ROS-injured synoviocytes recruit inflammatory cells to TMJ-OA lesions remains unclear. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the mRNA expression of chemoattractant molecules. The phosphorylation levels of intracellular signaling molecules were evaluated using western blot analysis. RESULTS: Hydrogen peroxide (H2O2) treatment significantly promoted mRNA expression of neutrophil chemoattractant CXCL15/Lungkine in a dose-dependent manner (100-500 µM) in fibroblast-like synoviocytes (FLSs) derived from mouse TMJ. H2O2 (500 µM) significantly upregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 in FLSs. Intriguingly, the mitogen-activated protein (MAP)/ERK kinase (MEK) inhibitor U0126 (10 µM) nullified H2O2-induced increase in CXCL15/Lungkine mRNA expression. Additionally, H2O2 (500 µM) administration significantly upregulated OH∙ production in FLSs, as assessed by live-cell permeant fluorescent probe targeted against OH∙ under fluorescence microscopy. Furthermore, the ROS inhibitor N-acetyl-l-cysteine (5 mM) partially but significantly reversed H2O2-mediated phosphorylation of ERK1/2. CONCLUSIONS: H2O2-induced oxidative stress promoted the expression of CXCL15/Lungkine mRNA in a MEK/ERK-dependent manner in mouse TMJ-derived FLSs, suggesting that FLSs recruit neutrophils to TMJ-OA lesions through the production of CXCL15/Lungkine and exacerbate the local inflammatory response.

3D digital analysis of magnetic force-driven orthodontic tooth movement.

With the introduction of rare earth magnets like neodymium-iron-boron (NdFeB), it has become possible to produce small magnets with high forces, necessary for its usage in the field of dentistry, such as for orthodontic tooth movement. The ultimate goal of this project is to establish magnetic force-driven orthodontic treatment as a future treatment modality for comprehensive orthodontic treatment. In order to utilize magnets for orthodontic treatment, we must first understand the characteristics of tooth movement created by magnetic forces. In this study, we aimed to digitally assess the efficacy of magnetic attraction and repulsion forces by means of a 3D digital analysis of movement (distance, direction, angulation and duration) and rotation (yaw, pitch and roll) of the crown and root of teeth in an ex vivo typodont model. We performed space closure and space gain treatment of maxillary central incisors (n = 30) and analyzed the movement and rotation of the teeth and root apex with 3D digital analysis. The results of the typodont model indicated significant differences on amount, speed and rotation of tooth and root movement created by magnetic attraction and repulsion forces. We also mimicked a moderate crowding typodont case and successfully treated it with a combination of attraction and repulsion magnetic forces. The moderate crowding case utilized magnets and a titanium archwire to guide the planned tooth movements and prevent undesired or unexpected movement. Further ex vivo experiments and considerations for biosafety will be necessary to investigate magnet force-driven orthodontics as a future modality of orthodontic treatment.

Cephalometric Measurements Of Non-Syndromic Oligodontia In Early Dental Age In A Japanese Population.

PURPOSE: Oligodontia significantly affects oral function and esthetics. Recognition of skeletal and dental patterns may aid in proper diagnosis and development of appropriate interventions. The aim of this study was to analyze skeletal and dental patterns for pre-adolescent patients with a diagnosis of oligodontia. PATIENTS AND METHODS: This study included 19 oligodontia patients (age: 9.5±1.3, Hellman's developmental stage IIIA~IIIB) along with a control group that comprised of 19 participants (age: 9.9±1.6) without any skeletal disharmony or congenitally missing teeth, with an Angle class I relationship and general crowding. Average cephalometric measurements among the oligodontia group were compared to the control group. The correlation between number of congenitally missing teeth (CMT) and each measurement was investigated. Skeletal measurements for both male and female patients in the oligodontia group and the control group were also compared. RESULTS: No significant difference between the experimental and the control group was observed with respect to skeletal angular and linear measurements, except the gonial angle. Differences in dental pattern measurements were observed. The oligodontia group had significantly smaller Mo-Ms and Is-Mo than the control group (p<0.01). No correlation was detected between severity of oligodontia (number of CMT) and skeletal measurement except for SNB (R=-0.4). For females with oligodontia, Mo-Ms (eruption of maxillary first molar) and Is-Mo (mesial location of maxillary first molar) significantly differed from females in the control group (p<0.01). In contrast, no differences in Mo-Ms or Is-Mo were detected for male patients when oligodontia and control group were compared. CONCLUSION: Among pre-adolescent Japanese patients with oligodontia in Hellman's developmental age IIIA~IIIB, no significant differences in skeletal characteristics were established when compared to the control group. However, tooth position of maxillary first molars indicated smaller vertical descent and mesial shift, which may suggest weak maxillary vertical development.

Characterization of PAX9 variant P20L identified in a Japanese family with tooth agenesis.

Transcription factors PAX9 and MSX1 play crucial roles in the development of permanent teeth at the bud stage, and their loss-of-function variants have been associated with congenital tooth agenesis. We sequenced the coding regions of the PAX9 and MSX1 genes from nine patients with non-syndromic tooth agenesis, and identified a missense mutation, P20L, of PAX9 in a single familial case involving three patients in two generations. Identical mutation was previously reported by other authors, but has not been characterized in detail. The mutation was located in a highly conserved N-terminal subdomain of the paired domain and co-segregated as a heterozygote with tooth agenesis. The patients showed defects primarily in the first and second molars, which is typical for cases attributable to PAX9 mutation. Luciferase reporter assay using the 2.3-kb promoter region of BMP4 and electrophoretic mobility shift assay using the CD19-2(A-ins) sequence revealed that P20L substitution eliminated most of the transactivation activity and specific DNA binding activity of PAX9 under the experimental conditions we employed, while some residual activity of the mutant was evident in the former assay. The hypomorphic nature of the variant may explain the relatively mild phenotype in this case, as compared with other PAX9 pathogenic variants such as R26W.