The 100 Most-Cited Randomised Controlled Trials in Orthodontics: A Bibliometric Study.

INTRODUCTION AND AIM: Randomised controlled trials (RCTs) are recognised as the highest level of original evidence and provide essential evidence for dentists to practice evidence-based dentistry. By analysing the top 100 most-cited RCT reports in orthodontics, this study aimed to determine popular research topics, key authors, countries, journals, and their impacts. METHODS: A comprehensive search was performed in the Web of Science (WoS) electronic database to identify the top 100 most-cited RCT reports in orthodontics. Publication and citation data were retrieved and further analysed and visualised using R Biblioshiny. The primary themes of the 100 articles were also determined. Additionally, the correlation between number of years since publication and citation counts was examined. RESULTS: The top 100 most-cited RCT reports were published between 1992 and 2018, contributed by 419 authors across 22 journals, with an average citation count of 93.48. The US led with the highest number of publications (28) and citations (2552), followed by the UK (22 and 2061) and Australia (8 and 912). Notably, 20 of the top 24 authors with at least 4 publications are from the UK. The primary focus areas of the articles included early Class II treatment (n = 14), obstructive sleep apnoea (n = 14), demineralisation (n = 12), and pain and quality of life (n = 12). Besides, a positive correlation was found between the number of years since publication and citation counts (P < .001). CONCLUSIONS: The top 100 most-cited RCT reports in orthodontics encompass a wide range of topics with varying focus areas across different time periods. This analysis recognises the contributions of scholars and offers valuable insights into the research trends within the field of orthodontics.

Aging-related decrease of histone methyltransferase SUV39H1 in adipose-derived stem cells enhanced SASP.

Aging-related diseases are closely associated with the state of inflammation, which is known as "inflammaging." Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed the senescence-associated secretory phenotype (SASP). Epigenetic regulation, especially the structural regulation of chromatin, is closely linked to the regulation of SASP. In our previous study, the suppressor of variegation 3-9 homolog 1 (SUV39H1) was elucidated to interact with Lhx8 and determine the cell fate of mesenchyme stem cells. However, the function of SUV39H1 during aging and the underlying mechanism of its epigenetic regulation remains controversial. Therefore, the C57BL/6 J CAG-Cre; SUV39H1fl/fl knockout mice and irradiation-induced cellular senescence model were built in this study to deepen the understanding of epigenetic regulation by SUV39H1 and its relation to SASP. In vivo and in vitro studies demonstrated that SUV39H1 decreased with aging and served as an inhibitor of SASP, especially IL-6, MCP-1, and Vcam-1, by altering H3K9me3 enrichment in their promoter region. These results provide new insights into the epigenetic regulation of SASP.

Effects of probiotics on the oral health of patients undergoing orthodontic treatment: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The effect of probiotics on oral health maintenance in orthodontic patients remains controversial. The aim of the study is to systematically review and assess the effects of probiotics on the oral health and microbiome of patients undergoing orthodontic treatment. SEARCH METHODS AND SELECTION CRITERIA: Databases including PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov, and ProQuest Dissertations & Theses Global databases were searched from their inception until June 2022. Randomised controlled trials that assessed the effects of probiotics on clinical and microbial outcomes in patients undergoing orthodontic treatment were included. DATA COLLECTION AND ANALYSIS: Data screening and collection were performed, and the risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The meta-analysis evaluated the effects of probiotics on Streptococcus mutans (S. mutans) and Lactobacillus counts. The quality of the evidence from the meta-analyses was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 405 records were identified, of which 15 studies were included in the qualitative synthesis and 4 in the meta-analysis. The patients in all the included studies were treated with fixed orthodontic appliances. Results regarding clinical outcomes were controversial; four out of five studies reported no significant changes in plaque in the probiotic group (P > .05), and two out of three studies reported no significant changes in the gingival index (P > .05). Regarding microbial outcomes, the meta-analysis results revealed that probiotics significantly increased the likelihood of reducing the abundance of S. mutans to below 105 CFU/ml (risk ratio: 2.05 [1.54, 2.72], P < .001) and reduced the likelihood of increasing the abundance of S. mutans to beyond 106 CFU/ml (risk ratio: 0.48 [0.28, 0.83], P = .009). However, the quality of evidence according to the GRADE was moderate. CONCLUSIONS AND IMPLICATIONS: There is insufficient evidence to determine the clinical benefits of probiotics as a supplement for the oral health of patients undergoing orthodontic treatment. However, probiotics may have benefits in reducing the salivary S. mutans counts in orthodontic patients. REGISTRATION: PROSPERO (CRD42022366650).

The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration.

Periodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the "gold standard" treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk-benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.

Effects of Two-Phase Treatment with Functional Appliances Followed by Extraction versus One-Phase Treatment with Extraction in Class II Growing Patients: A Case-Control Study.

Objectives: Fixed appliance treatment with premolar extraction is often required after functional appliance treatment to relieve crowding and improve facial aesthetics in the Asian population. This study compared the treatment efficacy of two approaches for treating Class II division 1 malocclusion: functional appliance followed by fixed appliance treatment with extraction (two-phase) and fixed appliance treatment with extraction (one-phase). Methods: Growing skeletal Class II patients with an overjet of ≥6 mm treated with two- or one-phase orthodontics were included. The two groups consisted of 29 patients (mean age = 12.55) and 30 patients (mean age = 12.72), respectively. Pre- and post-treatment cephalograms were analysed and skeletal, dental, and soft tissue characteristics were compared using independent t-tests. Treatment changes were compared within and between groups using paired and independent t-tests, respectively. Stepwise discriminant analysis was performed to identify the variables that best predicted pre-treatment group allocations. Results: At baseline, there were no significant between-group differences in age, gender, cervical vertebral maturation, or overjet. The two-phase group had greater Class II skeletal discrepancies (ANB angle and Wits appraisal). During treatment, the two-phase group showed greater improvements in intermaxillary relationship and facial convexity compared with the one-phase group (p < 0.01). Following treatment, the two-phase group had a greater L1/APog distance (p < 0.05). Facial convexity and Wits appraisal were identified as parameters significantly influencing the clinicians' decision to use a one- or two-phase approach. Conclusions: In patients requiring premolar extraction, two-phase (vs. one-phase) treatment produced greater improvements in the intermaxillary relationship and facial convexity.

Mechanosensitive Piezo1 and Piezo2 ion channels in craniofacial development and dentistry: Recent advances and prospects.

Mechanical forces play important roles in many biological processes and there is increasing interest and understanding of these roles. Mechanotransduction is the process by which mechanical stimuli are converted to biochemical signals through specific mechanisms, and this results in the activation of downstream signaling pathways with specific effects on cell behaviors. This review systematically summarizes the current understanding of the mechanosensitive Piezo1 and Piezo2 ion channels in craniofacial bone, tooth, and periodontal tissue, presenting the latest relevant evidence with implications for potential treatments and managements of dental and orofacial diseases and deformities. The mechanosensitive ion channels Piezo1 and Piezo2 are widely expressed in various cells and tissues and have essential functions in mechanosensation and mechanotransduction. These channels play an active role in many physiological and pathological processes, such as growth and development, mechano-stimulated bone homeostasis and the mediation of inflammatory responses. Emerging evidence indicates the expression of Piezo1 and Piezo2 in bone, dental tissues and dental tissue-derived stem cells and suggests that they function in dental sensation transduction, dentin mineralization and periodontal bone remodeling and modulate orthodontic tooth movement.

Temporal induction of Lhx8 by optogenetic control system for efficient bone regeneration.

BACKGROUND: The spatiotemporal regulation of essential genes is crucial for controlling the growth and differentiation of cells in a precise manner during regeneration. Recently, optogenetics was considered as a potent technology for sophisticated regulation of target genes, which might be a promising tool for regenerative medicine. In this study, we used an optogenetic control system to precisely regulate the expression of Lhx8 to promote efficient bone regeneration. METHODS: Quantitative real-time PCR and western blotting were used to detect the expression of Lhx8 and osteogenic marker genes. Alkaline phosphatase staining and alizarin red staining were used to detect alkaline phosphatase activity and calcium nodules. A customized optogenetic expression system was constructed to regulate Lhx8, of which the expression was activated in blue light but not in dark. We also used a critical calvarial defect model for the analysis of bone regeneration in vivo. Moreover, micro-computed tomography (micro-CT), three-dimensional reconstruction, quantitative bone measurement, and histological and immunohistochemistry analysis were performed to investigate the formation of new bone in vivo. RESULTS: During the osteogenic differentiation of BMSCs, the expression levels of Lhx8 increased initially but then decreased thereafter. Lhx8 promoted the early proliferation of BMSCs but inhibited subsequent osteogenic differentiation. The optogenetic activation of Lhx8 in BMSCs in the early stages of differentiation by blue light stimulation led to a significant increase in cell proliferation, thus allowing a sufficient number of differentiating BMSCs to enter the later osteogenic differentiation stage. Analysis of the critical calvarial defect model revealed that the pulsed optogenetic activation of Lhx8 in transplanted BMSCs over a 5-day period led to a significant increase in the generation of bone in vivo. CONCLUSIONS: Lhx8 plays a critical role in balancing proliferation and osteogenic differentiation in BMSCs. The optogenetic activation of Lhx8 expression at early stage of BMSCs differentiation led to better osteogenesis, which would be a promising strategy for precise bone regeneration.

FGF8 and BMP2 mediated dynamic regulation of dental mesenchyme proliferation and differentiation via Lhx8/Suv39h1 complex.

The homeobox gene, LIM-homeobox 8 (Lhx8), has previously been identified as an essential transcription factor for dental mesenchymal development. However, how Lhx8 itself is regulated and regulates odontogenesis remains poorly understood. In this study, we employed an RNAscope assay to detect the co-expression pattern of Lhx8 and Suv39h1 in the dental mesenchyme, which coincided with the dynamic expression profiles of the early epithelium signal of Fibroblast Growth Factor 8 (FGF8) and the later mesenchymal signal Bone Morphogenetic Protein 2 (BMP2). Moreover, FGF8 activated Lhx8, whereas BMP2 repressed Lhx8 expression at the transcriptional level. The high expression of Lhx8 in the early dental mesenchyme maintained the cell fate in an undifferentiated status by interacting with Suv39h1, a histone-lysine N-methyltransferase constitutively expressed in the dental mesenchyme. Further in the ex vivo organ culture model, the knockdown of Suv39h1 significantly blocked the function of Lhx8 and FGF8. Mechanistically, Lhx8/Suv39h1 recognized the odontoblast differentiation-related genes and repressed gene expression via methylating H3K9 on their promoters. Taken together, our data here suggest that Lhx8/Suv39h1 complex is inversely regulated by epithelium-mesenchymal signals, balancing the differentiation and proliferation of dental mesenchyme via H3K9 methylation.

Control of mesenchymal stem cell biology by histone modifications.

Mesenchymal stem cells (MSCs) are considered the most promising seed cells for regenerative medicine because of their considerable therapeutic properties and accessibility. Fine-tuning of cell biological processes, including differentiation and senescence, is essential for achievement of the expected regenerative efficacy. Researchers have recently made great advances in understanding the spatiotemporal gene expression dynamics that occur during osteogenic, adipogenic and chondrogenic differentiation of MSCs and the intrinsic and environmental factors that affect these processes. In this context, histone modifications have been intensively studied in recent years and have already been indicated to play significant and universal roles in MSC fate determination and differentiation. In this review, we summarize recent discoveries regarding the effects of histone modifications on MSC biology. Moreover, we also provide our insights and perspectives for future applications.

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release.

Tooth defect and tooth loss are common clinical diseases in stomatology. Compared with the traditional oral restoration treatment, tooth regeneration has unique advantages and is currently the focus of oral biomedical research. It is known that dozens of cytokines/growth factors and other bioactive factors are expressed in a spatial-temporal pattern during tooth development. On the other hand, the technology for spatial-temporal control of drug release has been intensively studied and well developed recently, making control release of these bioactive factors mimicking spatial-temporal pattern more feasible than ever for the purpose of tooth regeneration. This article reviews the research progress on the tooth development and discusses the future of tooth regeneration in the context of spatial-temporal release of developmental factors.

Optogenetic control of mesenchymal cell fate towards precise bone regeneration.

Rationale: Spatial-temporal control of cell fate in vivo is of great importance for regenerative medicine. Currently, there remain no practical strategies to tune cell-fate spatial-temporally. Optogenetics is a biological technique that widely used to control cell activity in genetically defined neurons in a spatiotemporal-specific manner by light. In this study, optogenetics was repurposed for precise bone tissue regeneration. Methods: Lhx8 and BMP2 genes, which are considered as the master genes for mesenchymal stem cell proliferation and differentiation respectively, were recombined into a customized optogenetic control system. In the system, Lhx8 was constitutively expressed, while BMP2 together with shLhx8 expression was driven by blue light. Results: As expected, blue light induced BMP2 expression and inactivated Lhx8 expression in cells infected with the optogenetic control system. Optogenetic control of BMP2 and Lhx8 expression inversely regulates MSC fate in vitro. By animal study, we found that blue light could fine-tune the regeneration in vivo. Blue light illumination significantly promotes bone regeneration when the scaffold was loaded with MSCs infected with adeno-Lhx8, GI-Gal4DBD, LOV-VP16, and BMP2-shLhx8. Conclusions: Together, our study revealed that optogenetic control of the master genes for mesenchymal stem cell proliferation and differentiation would be such a candidate strategy for precise regenerative medicine.