Epigenetic regulation of osteogenic differentiation of periodontal ligament stem cells in periodontitis.

Periodontitis is an inflammatory disease characterized by alveolar bone loss. Periodontal ligament stem cells (PDLSCs) have osteogenic differentiation potential, which can be influenced by epigenetics regulation in periodontitis. Therefore, this review aimed to shed light on the role of different epigenetic mechanisms in the osteogenic differentiation of PDLSCs and to consider the prospects of their possible therapeutic applications in periodontitis. Databases MEDLINE (through PubMed) and Web of Science were searched for the current knowledge of epigenetics in osteogenic differentiation of PDLSCs using the keywords "periodontal ligament stem cells", "epigenetic regulation", "epigenetics", "osteogenic differentiation", and "osteogenesis". All studies introducing epigenetic regulation and PDLSCs were retrieved. This review shows that epigenetic factors like DNMT, KDM6A, HDACi, some miRNAs, and lncRNAs can induce the osteogenic differentiation of PDLSCs in the noninflammatory microenvironment. However, the osteogenic differentiation of PDLSCs is inhibited in the inflammatory microenvironment through the upregulated DNA methylation of osteogenesis-related genes and specific changes in histone modification and noncoding RNA. Epigenetics of osteogenic differentiation of PDLSCs in inflammation exhibits the contrary effect compared with a noninflammatory environment. The application of epigenetic drugs to regulate the abnormal epigenetic status in periodontitis and focus on alveolar bone regeneration is promising.

Roles of DNA methylation in influencing the functions of dental-derived mesenchymal stem cells.

OBJECTIVE: DNA methylation as intensively studied epigenetic regulatory mechanism exerts pleiotropic effects on dental-derived mesenchymal stem cells (DMSCs). DMSCs have self-renewal and multidifferentiation potential. Here, this review aims at summarizing the research status about application of DMSCs in tissue engineering and clarifying the roles of DNA methylation in influencing the functions of DMSCs, with expectation of paving the way for its in-depth exploration in tissue engineering. METHOD: The current research status about influence of DNA methylation in DMSCs was acquired by MEDLINE (through PubMed) and Web of Science using the keywords 'DNA methylation', 'dental-derived mesenchymal stem cells', 'dental pulp stem cells', 'periodontal ligament stem cells', 'dental follicle stem cells', 'stem cells from the apical papilla', 'stem cells from human exfoliated deciduous teeth', and 'gingival-derived mesenchymal stem cells'. RESULTS: This review indicates DNA methylation affects DMSCs' differentiation and function through inhibiting or enhancing the expression of specific gene resulted by DNA methylation-related genes or relevant inhibitors. CONCLUSION: DNA methylation can influence DMSCs in aspects of osteogenesis, adipogenesis, immunomodulatory function, and so on. Yet, the present studies about DNA methylation in DMSCs commonly focus on dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Little has been reported for other DMSCs.

Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins.

OBJECTIVES: To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation. MATERIALS AND METHODS: We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague-Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells. RESULTS: A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague-Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased. CONCLUSIONS: FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation. CLINICAL RELEVANCE: This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.

Effects of bonded spurs, fixed and removable palatal crib in the early treatment of anterior open bite: A systematic review and meta-analysis.

INTRODUCTION: Bonded spurs, fixed or removable palatal cribs have been used to treat anterior open bite (AOB) in growing children. Different conclusions have been brought out by different authors. This meta-analysis aimed to evaluate the effect of bonded spurs, fixed and removable palatal cribs in the early treatment of AOB. METHODS: A comprehensive electronic search was carried out through PubMed, Embase (via Ovid), MEDLINE (via Ovid), Cochrane Central Register of Controlled Trials, and Web of Science up to May 1, 2022. This meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The work was carried out by 2 reviewers in duplicate and independently, including electronic searching, data extracting, risk of bias assessment, quality of evidence grading, heterogeneity and statistical power analysis, and eligibility evaluation of the retrieved articles. RESULTS: Four studies out of 181 articles were recruited in the meta-analysis after applying the inclusion and exclusion criteria. The results showed that bonded lingual spurs and fixed palatal crib or spurs produced similar overbite changes (mean difference, -0.32; 95% confidence interval, -1.06 to 0.43; P = 0.41; I2 = 27%; meta power = 0.099). Fixed palatal crib and removable palatal crib also exhibited comparable effects in correcting AOB (mean difference, -0.02; 95% confidence interval, -0.90 to 0.86; P = 0.96; I2 = 0%; meta power = 0.2182). The quality of evidence about these 2 outcomes assessed with GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was low. CONCLUSIONS: Bonded lingual spurs, fixed palatal crib or spurs, and removable palatal crib had similar effects in the early treatment of AOB. Because the number of included studies was limited and only the overbite changes before and after treatment were assessed, more clinical randomized controlled studies with longer follow-ups are needed to get more clinically significant advice.

Effect of tetracyclines on pulpal and periodontal healing after tooth replantation: a systematic review of human and animal studies.

BACKGROUND: Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation. METHODS: A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing. CONCLUSIONS: As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions.

Management of ectopically erupting permanent molars in a seven-year-old girl: A case report.

Ectopic eruption of permanent first molar is a developmental disturbance, leading to many local problems, such as premature loss of the second primary molars, space loss, increased prevalence of dental caries, supraeruption of the opposing molars, mesial inclination of the permanent maxillary first molars and class II molar relationship. We report the case of a seven-and-a-half-year-old girl with ectopic eruption of permanent maxillary and mandibular first molar, treated by orthodontic separators and slicing the distal surface of the adjacent primary second molar separately. Regular examination and timely interception are important during oral health management of children and is of great significance in alleviating the side effects of ectopic eruption.

Expression of proteins of elastic fibers and collagen type I in orthodontically rotated teeth in rats.

INTRODUCTION: The aims of this study were to investigate the expression of proteins of elastic fibers and collagen type I in the supra-alveolar structure of orthodontically rotated teeth in rats and to elucidate whether circumferential supracrestal fiberotomy diminishes relapse. METHODS: The rats' maxillary left first molars were rotated by couple of force. Specimens were divided into groups according to different orthodontic procedures. A1-3 and B1-3 were blank control groups and operation control groups. Group C underwent rotation only, and group D was treated with rotation and retention. Groups E and F were treated with rotation, retention, and release of retention; additionally, circumferential supracrestal fiberotomy was performed in group F before the release of retention. The animals were killed, and the jaws were processed for histologic evaluation using the immunohistochemical method to evaluate the protein expressions of elastin, fibrillin-1, fibrillin-2, and collagen type I in supra-alveolar structures (around and below the gingival sulcus) between the maxillary left first and second molars. The degree and percentage of relapse were measured by a series of impressions. RESULTS: The degree and percentage of relapse in group F were much lower than those in group E (P <0.05). Collagen type I was increased in group C (P <0.05) and at normal levels in groups D, E, and F. Elastin below the gingival sulcus and fibrillin-1 showed the same patterns of expression and were consistently elevated in groups C, D, E, and F (P <0.05). No positive staining for elastin was found around the gingival sulcus in any specimen. The difference in the expression of fibrillin-2 between the experimental groups (C, D, E, and F) and their matching control groups was not statistically significant (P >0.05). CONCLUSIONS: Circumferential supracrestal fiberotomy can alleviate the relapse of rotated teeth. Collagen fibers of supra-alveolar structures might contribute to relapse in a short time, whereas elastic fibers may be the reason that rotated teeth relapse to their original positions after retention.

Protein and mRNA expressions of IL-6 and its key signaling factors under orthodontic forces in mice: An in-vivo study.

INTRODUCTION: The purpose of this study was to investigate the mechanical loading-induced changes in protein and mRNA expressions of interleukin-6 (IL-6) and its key signaling factors glycoprotein 130 (gp130), signal transducer and activator of transcription 3 (STAT3), and the Src homology phosphotyrosine phosphatase (SHP2) at the tension and compression sides of the teeth in mouse models. METHODS: A total of 55 C57B/6 mice (10 weeks old) were divided into 3 groups. Orthodontic force was applied in group A (experimental group, n = 30); the tooth movement device was placed without activation in group B (sham control group, n = 15), and group C (blank control group, n = 10). Tooth movement was induced by a nickel-titanium coil spring inserted between the maxillary left incisor and the first molar with a force of approximately 4 g. The animals were killed 12 days after the interventions; protein and mRNA expressions of IL-6, gp130, STAT3, and SHP2 in the periodontal tissues were observed with immunohistochemistry and in-situ hybridization, respectively. RESULTS: In contrast with the control groups, we observed enhanced expressions of IL-6, gp130, STAT3, and SHP2 protein and mRNA at the mesial and distal sides of the teeth with application of orthodontic forces in the experimental group. In contrast with the distal side, we observed enhanced expression of gp130 protein and mRNA at the mesial side in the experimental group. CONCLUSIONS: We observed enhanced expression of IL-6 and its key signaling factors gp130, STAT3, and SHP2 protein and mRNA at the tension and compression sides of the teeth with application of orthodontic forces. The mechanical loading applied for orthodontic tooth movement might induce changes in protein localization and mRNA expression patterns of IL-6 and its key signaling factors gp130, STAT3, and SHP2 at the tension and compression sides of the periodontal ligaments of the teeth in mouse models. The result might demonstrate the special role of IL-6 and its key signaling factors in the alveolar bone-modeling process.

Progressive destruction of jaws caused by the delayed treatment of Langerhans cell histiocytosis in a 2-year-old boy: A case report.

Langerhans cell histiocytosis (LCH) is a disease with varied clinic manifestations. The oral symptoms and signs of LCH localized to the jaws are nonspecific, which may lead to misdiagnosis of this disease. The purpose of this paper was to present the case of a 2-year, 4-month-old LCH patient with progressive destruction of jaws caused by the delayed treatment due to the global outbreak of COVID-19. The cone beam CT analysis after an interval of 6 months reminded us the great significance of early diagnosis and treatment of LCH.

IL-1α Regulates Osteogenesis and Osteoclastic Activity of Dental Follicle Cells Through JNK and p38 MAPK Pathways.

Inflammatory cytokines such as interleukin-1α (IL-1α) are increased in teeth with periapical lesions. Primary teeth with periapical lesions have a propensity for accelerated eruption of the successors. In this study, we asked whether increased levels of IL-1α in the dental follicle (DF) occurring as the result of periapical lesions promote tooth eruption, possibly due to enhanced osteoclastic remodeling of DF cells (DFCs). To this end, we studied the effect and possible mechanism of IL-1α on osteogenic differentiation, osteoclastogenic activity, and matrix remodeling of DFCs. Results demonstrated that DFCs cultured with IL-1α exhibited reduced osteogenic capacity, higher osteoclastogenic activity, and stronger invasive ability. Phosphorylation of JNK and p38 was upregulated, and pretreatment with SB203580 and SP600125 reversed the effect of IL-1α on DFCs. Neonatal rats subjected to subcutaneous injection of an IL-1 receptor antagonist exhibited a reduced number in activated osteoclasts, increased expression of alkaline phosphatase and osteopontin, and delayed tooth eruption. These data support our hypothesis that increased IL-1α cytokine levels as they occur during periodontal and periapical inflammation cause osteoclastic remodeling of the alveolar socket as a requirement for tooth eruption and thus may indirectly promote the vertical eruption of teeth toward the occlusal plane.

Common dental diseases in children and malocclusion.

Malocclusion is a worldwide dental problem that influences the affected individuals to varying degrees. Many factors contribute to the anomaly in dentition, including hereditary and environmental aspects. Dental caries, pulpal and periapical lesions, dental trauma, abnormality of development, and oral habits are most common dental diseases in children that strongly relate to malocclusion. Management of oral health in the early childhood stage is carried out in clinic work of pediatric dentistry to minimize the unwanted effect of these diseases on dentition. This article highlights these diseases and their impacts on malocclusion in sequence. Prevention, treatment, and management of these conditions are also illustrated in order to achieve successful oral health for children and adolescents, even for their adult stage.

Effect of Low-Level Laser Therapy on Relapse of Rotated Teeth: A Systematic Review of Human and Animal Study.

OBJECTIVE AND BACKGROUND: Low-level laser therapy (LLLT) has been used to reduce the relapse of orthodontically rotated teeth. However, controversial conclusions have been drawn by different authors. This review aimed to evaluate the efficacy of LLLT on relapse of corrected tooth rotations systematically by overall search of available studies and scientific assessment. METHODS: A comprehensive electronic search was performed through PubMed, MEDLINE, EMBASE, Web of Science, CENTRAL, PRL, and WHO ICTRP up to November 2015 with no language limitation. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Risk of bias assessment was undertaken according to Cochrane Handbook for Systematic Reviews of Interventions. Two review authors conducted the work of search, selection, and quality assessment independently in duplicate. RESULTS: Out of 112 studies, two animal experiments and one human study were included. Degree and percentage of relapse of rotated teeth were compared between control and LLLT group. CONCLUSIONS: According to the results of our systematic review, the effect of LLLT on relapse of corrected tooth rotations is related to energy density. Namely, low energy density seems to promote relapse, while high energy density might alleviate the relapse. Since available investigations are limited, more well-designed randomized controlled trials involving humans are needed to get more clinically significant conclusions.

[Investigation of differences in subjective demand for orthodontic treatment of middle school students in zones with different economic levels].

OBJECTIVE: To investigate the acquaintance to orthodontics and possible factors that obstruct orthodontic treatment in middle school students in zones with different economic levels in Jiangjin, Chongqing. METHODS: The students were randomly divided into four groups: A class from a junior high school in town (group 1), a class from a senior high school in town (group 2), a class from a junior high school in the countryside (group 3), a class from a senior high school in the countryside (group 4). The information was collected by questionnaire, and the statistical analysis of results was carried out by SPSS 17.0 software. RESULTS: Sex made difference in the acquaintance to orthodontics treatment. Girls worried more about teeth extraction and pain that may occur during treatment than the boys. Students in the city had more access to related consultations compared to those in the countryside. Different economic conditions made much contribution to the proportion to go for orthodontics treatment in cities and rural areas. The evaluation from families and friends may affect patients' subjective estimation to themselves. CONCLUSION: Orthodontists should learn more about student patiens from various aspects, and make different therapies according to their sexes, economic conditions of family, education levels, etc. Only so can orthodontists get better compliance from their patients.