Mesenchymal stem cells (MSCs) are obtained from deciduous teeth noninvasively, attracting attention as a promising source for regenerative cell-based medicine. However, cellular heterogeneity of MSCs, such as differences in differentiation potential, is one of the main issues in its clinical applications. Therefore, establishing an efficient strategy inducing uniform cell differentiation is essential for efficient regenerative therapy. Since maintaining bone integrity is critical in preventing various oral diseases, we attempted to develop an effective approach of osteoblast differentiation from MSCs and preosteoblast cells. Previous studies demonstrated that proteasome inhibitors, a therapeutic agent for multiple myeloma, improve osteoclastic bone lesions and increase osteoblastic markers in patients with multiple myeloma. These studies prompted us to analyze proteasome-dependent regulation of osteoblast differentiation signals. To this end, we focused on Osterix (Osx/Sp7) protein, a transcription factor essential for osteoblast differentiation. We investigated the Osx protein degradation mechanism and its involvement in osteoblast differentiation using a pharmaceutical approach and obtained the following findings.

1. Simultaneous treatment of preosteoblasts and MSCs with low concentrations of bone morphogenetic protein (BMP) and proteasome inhibitors leads to synergistic enhancement of osteoblast differentiation and post-translational modification-dependent stabilization of Osx protein.

2. The Skp1-Cullin1-F-box protein (SCF)^Fbw7 complex serves as an E3 ligase for Osx protein degradation.

3. p38-mediated Osx phosphorylation facilitates the interaction between Osx and SCF^Fbw7.

4. p38 inhibitor-treated MSCs, Fbw7 knockdown MSCs, and Fbw7 knockout mouse-derived osteoblast progenitor cells show the accumulation of Osx protein and increased cell differentiation compared to control cells.

5. Introduction of p38 phosphorylation-deficient Osx mutant in Osx knockout cells significantly increases osteoblast differentiation compared to wild-type Osx.

These results suggest that regulating Osx protein stability through the Fbw7/p38 pathway may be critical in controlling bone metabolism by suppressing osteoblast differentiation.

Actinomyces oris, one of the initial colonizers, attaches to tooth surfaces and forms biofilms via the fimbriae expressed on its surface. Many oral bacteria produce short-chain fatty acids (SCFAs) as metabolites during growth. These SCFAs have been detected in human saliva and dental plaque. SCFAs have been shown to promote biofilm formation and the initial attachment and colonization of Actinomyces naeslundii. However, the relationship between SCFAs and A. oris has not been clarified. In this study, we investigated the effects of SCFAs on A. oris biofilm formation and initial attachment and colonization, including the relationship between SCFAs and the fimbriae of A. oris. The results showed that butyric acid and propionic acid promoted FimA-dependent biofilm formation by A. oris. Furthermore, a mixture of acetic acid, butyric acid, and propionic acid, which are SCFAs produced in dental plaque, promoted the initial attachment and colonization of A. oris via FimA-dependent and FimA-independent mechanisms. Furthermore, the results suggested that non-ionized acids were involved in this phenomenon.

Helicobacter pylori, a Gram-negative microaerophilic bacterium, causes gastric diseases and can be transmitted via the oral cavity, though factors required for its colonization are largely unknown. Although a relationship between H. pylori infection and clinical periodontal status has been shown by comparing the distribution frequency of the bacterium in healthy subjects with that in periodontal disease patients, differences in the periodontopathic bacterial species in the oral cavity of H. pylori-positive and -negative subjects remain to be elucidated. The present study was conducted to examine the relationship of the presence of H. pylori in the oral cavity with that of major periodontopathic bacterial species. Periodontal pocket depths in 39 subjects were determined. Then, PCR examinations were performed to detect H. pylori and other bacterial species in saliva, dental plaque, and dental pulp specimens. The results showed that periodontal pockets were significantly deeper in the H. pylori-positive as compared to the -negative subjects. Furthermore, Porphyromonas gingivalis, a major periodonotopathic pathogen, was detected at a significantly higher frequency in the H. pylori-positive dental plaque specimens. An important pathogenic factor of P. gingivalis is an approximately 41-kDa filamentous appendage (FimA) that is encoded by fimA genes, classified as genotypes Ⅰ to Ⅴ and Ⅰb, expressed on the cell surfaces. When the distribution frequencies of fimA genotypes in subjects with or without H. pylori in the oral cavity were compared, type Ⅱ fimA was detected at a significantly higher frequency in the H. pylori-positive subjects. It was concluded that there is an association of H. pylori presence in the oral cavity with deteriorated periodontal condition.

Recently, the number of children with traumatic injuries to their teeth has increased compared to our department's survey of 30 years ago. To identify the trends in patients presenting with trauma to the oral-facial region and in the treatments being used for this trauma, we surveyed 227 patients under 15 who visited the pediatric outpatient dentistry clinic of the Kanagawa Dental University Hospital for the first time complaining of trauma from 2016 to 2018.

The following key points were identified :

1. Pediatric patients complaining of traumatic injuries to the oral-facial region made up 14.1% of the total number of first-time patients at the Kanagawa Dental University Hospital pediatric outpatient clinic. Those with deciduous tooth injuries were 0-3 years old, and those with permanent tooth injuries were 7-9 years old.

2. The most frequent injuries were dislocations of deciduous teeth, an almost equal number of dislocations and fractures of permanent teeth, and lacerations in soft tissue.

3. The progress of injured teeth showed that 17.7% of deciduous teeth and 18.5% of permanent teeth had sequelae of trauma (discoloration, pathological tooth movement, pathological root resorption, root apex penetration, and eruption disturbance to the succeeding permanent tooth were confirmed by oral examination and X-ray examination, and one of these sequelae was observed in the cases with any of the above symptoms). The sequelae of trauma were predominantly due to concussion in deciduous teeth and incomplete dislocation in permanent teeth.

The majority of cases were treated at the time of initial examination, with concussion treated by follow-up observation and incomplete dislocation treated by reduction fixation. The results of this study indicated that concussion of deciduous teeth requires follow-up until replacement with permanent teeth, and incomplete dislocation of permanent teeth requires follow-up for at least one year after injury. Therefore, it is important to inform dental professionals, parents, and those involved in childcare and education about the need for long-term follow-up after injury.

Changes in the environment surrounding children and parents' needs for dental care, and regional characteristics are expected to have a significant impact on pediatric dental care. The aim of this study was to compare the results of a survey on the role of pediatric dentistry in university hospitals in collaboration with community health care providers and the state of pediatric dentistry in university hospitals in 2008 and 2018. The study showed the following findings:

1. The number of first-visit patients decreased in 2018, however, the proportion of school-age patients increased. The number and proportion of referred patients both increased.

2. The most common chief complaint was caries in both years, followed by regular check-up, caries prevention, and trauma, in order.

3. The distribution of chief complaints did not differ significantly among places of residence, except for high caries-related chief complaints in Yokohama City and low regular check-ups, caries prevention, and orthodontic complaints in Yokosuka City.

4.Caries-related chief complaints were the highest in the 3- to 5-year age group.

5. The chief complaint of abnormal eruption increased in referred patients.

6. Breast milk was the most common source of nutrition during lactation, with an average weaning time of 7 months in both years. In 2018, weaning completion time was 2 months later than in 2008. Breast milk was the most common source of nutrition after 18 months of weaning in both years.

These results indicated the importance of considering chronological changes in first-time patients in the Yokosuka and Miura areas in order to contribute to the healthy oral development of children. In addition, our mission is to provide highly specialized pediatric dental care in collaboration with local medical institutions while staying close to the lives of patients.

The patient was a 10-year-8-month-old boy who had severe root resorption of the adjacent maxillary lateral and central incisors reaching the pulpal chambers caused by ectopic impaction of the maxillary left canine. Those incisors had significant mobility. The dental follicle of the impacted canine was 3.5 mm thick and considered a dentigerous cyst. The canine cusp crossed the lateral incisor, Ericson's analysis of overlap of the root of the permanent incisors and the crown of the impacted canine was assessed as sector 4, and the angle of mesial inclination to the midline was 26.5°. More than 1/2 of the root length of the lateral incisor was resorbed, and the crown-to-root length ratio of the central incisor was 4 : 3, which was 64% of the root length of the contralateral central incisor. Since the ipsilateral mandibular lateral incisor was congenitally missing, we decided to extract the severely root-resorbed lateral incisor and to erupt the impacted canine distally to the central incisor.

Twelve months after the extraction of the deciduous canine and the permanent lateral incisor, the impacted canine spontaneously erupted, and the tooth axis was improved. Furthermore, as the apex of the canine was moved away from the root of the central incisor, root resorption of the central incisor stopped, regeneration of alveolar bone occurred, and tooth mobility disappeared.

The patient's oral findings at 2 years and 8 months after treatment were, including the rotation of the left maxillary canine, that malocclusion was minor. From X-ray images of the preserved maxillary left central incisor, an alveolar hard line was confirmed around the entire root circumference. Moreover, from CBCT images, it was confirmed that the root canal of the central incisor, which had been opened due to root resorption caused by the ectopically impacted canine, was tapered from the palatal to the labial direction due to the promotion of dentin formation in the dentin at the root tip and that an apical foramen had formed at the end.

These results suggest that the long-term prognosis of severely root-resorbed permanent incisors due to impacted canines may be improved by removing the cause. However, since root-resorbed incisors may become more mobile with age, careful oral management is considered necessary.