Nuclear import of transcriptional corepressor BCOR occurs through interaction with karyopherin α expressed in human periodontal ligament.

Mutations in the gene encoding BCL-6 corepressor (BCOR) are responsible for oculofaciocardiodental (OFCD) syndrome, which is a rare X-linked dominant disorder characterized by radiculomegaly of permanent teeth as the most typical symptom. To function as a transcriptional corepressor, BCOR needs to enter the nucleus; however, the molecular pathway for its nuclear translocation during dental root formation remains unclear. The purpose of this study was to determine the mechanism underlying BCOR transport into the nucleus. Our results showed that human periodontal ligament (PDL) cells expressed karyopherin α (KPNA)2, KPNA4, and KPNA6 belonging to a family of nuclear import proteins, which interacted with BCOR in the immunoprecipitation assay. Site-directed mutagenesis targeting the two nuclear localization signals (NLSs) within BCOR reduced its nuclear translocation; however, co-expression of KPNA2, KPNA4, or KPNA6 with BCOR carrying a previously described mutation which eliminated one of the two NLSs significantly increased nuclear accumulation of the mutant BCOR, indicating participation of KPNA in BCOR nuclear translocation. Comparative expression profiling of PDL cells isolated from normal and OFCD patients revealed significant downregulation of SMAD4, GLI1, and nuclear factor 1-C (NFIC) mRNA expression, suggesting that BCOR mutations cause hyperactive root formation in OFCD syndrome by inhibiting SMAD4-Hedgehog-NFIC signaling implicated in dental root development. Our study contributes to understanding of the mechanisms providing nuclear import of BCOR during root formation.

Case report: Long-term management of occlusion after surgical-orthodontic treatment for a patient with drug-induced open bite developed after the onset of schizophrenia.

Background: Schizophrenia is a major mental disorder, with an estimated incidence of 1%. Since they are sensitive to sensory changes, orthodontic treatment to move teeth should be avoided as aggressively as possible in these patients because of strong concerns about the possibility of causing adverse psychological effects, thus there are few reports on orthodontic treatment for schizophrenia patients. We report a case of severe open bite caused by medication after the onset of schizophrenia, even though the patient's occlusion had been stable for a long time after surgical orthodontic treatment. Medication control and the use of a minimally invasive orthodontic appliance improved the occlusion without adversely affecting the patient's mental health. Case: A 22-year-old woman presented to the clinic with a chief complaint of an anterior open bite. Intraoral findings showed an overbite (vertical overlap of the incisor teeth) of -3.0 mm and an overjet (horizontal overlap of the incisor teeth) of -0.5 mm. The preoperative orthodontic treatment included bilateral extraction of the maxillary first premolars. Subsequently, orthognathic surgery was performed to achieve a harmonized skeletal relationship and occlusion. Occlusion was stable for 3 years after surgery. However, 10 years after surgery, the patient returned to the clinic complaining of an anterior open bite (overbite = -4.0 mm). Six years prior to the return, the patient was diagnosed with schizophrenia. We thought that ignoring the patient's strong desire to treat her open bite might also cause psychological problems; therefore, in addition to medication control, we treated her using a minimally invasive removable orthodontic appliance (retainer with tongue crib). Her anterior open bite improved (overbite, +1.0 mm) to within the normal range. Conclusion: In this case, medication control was thought to be essential to improve her drug-induced open bite. However, minimally invasive orthodontic treatment, such as the use of a removable appliance, might be helpful in promoting her mental stability as well as for improving occlusion. Careful support is required to obtain information about the patient's mental state and medications through close cooperation with psychiatrists.

Combination of estrogen deficiency and excessive mechanical stress aggravates temporomandibular joint osteoarthritis in vivo.

OBJECTIVE: It has been suggested that degenerative conditions of the temporomandibular joint (TMJ), such as osteoarthritis (OA) and progressive condylar resorption, are caused by multiple etiological factors, such as hormonal imbalance and excessive mechanical stress. However, it is unclear whether these factors interrelate in the degenerative process of the condyle. The aim of this study was to observe the effects of combined hormonal imbalance and excessive mechanical stress on the condyle using a mouse model. MATERIALS AND METHODS: Ovariectomy (OVX) was performed in 8-week-old female mice. Three weeks after OVX, a build-up resin was bonded to the right maxillary molars to create imbalanced occlusion (increased occlusal vertical dimension, iOVD). Mice were divided into four groups: control, OVX, iOVD, and OVX + iOVD. RESULTS: Histomorphometric analysis showed the lowest cartilage thickness and the highest TMJ-OA score in the OVX + iOVD group. Bone structural analysis showed significantly lower subchondral bone mass in all experimental groups. Additionally, the OVX + iOVD group showed up-regulated osteoclastic activity and increased apoptosis in the condyle. Gene expression analysis showed significantly elevated expression of pre-inflammatory cytokines in the OVX + iOVD group. These data showed that the OVX + iOVD group exhibited the most severe inflammatory TMJ-OA. Upregulation of ERα and activation of the ERK pathway was observed in the OVX + iOVD group. CONCLUSIONS: Additive effects of estrogen deficiency and excessive mechanical stress on the condyle exacerbate TMJ-OA. Furthermore, estrogen deficiency and excessive mechanical stress combined may exacerbate TMJ-OA though activation of the ERK pathway.