Expert consensus on pediatric orthodontic therapies of malocclusions in children.

Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Long non-coding RNA LncTUG1 regulates favourable compression force-induced cementocytes mineralization via PU.1/TLR4/SphK1 signalling.

Orthodontic tooth movement (OTM) is a highly coordinated biomechanical response to orthodontic forces with active remodelling of alveolar bone but minor root resorption. Such antiresorptive properties of root relate to cementocyte mineralization, the mechanisms of which remain largely unknown. This study used the microarray analysis to explore long non-coding ribonucleic acids involved in stress-induced cementocyte mineralization. Gain- and loss-of-function experiments, including Alkaline phosphatase (ALP) activity and Alizarin Red S staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence analyses of mineralization-associated factors, were conducted to verify long non-coding ribonucleic acids taurine-upregulated gene 1 (LncTUG1) regulation in stress-induced cementocyte mineralization, via targeting the Toll-like receptor 4 (TLR4)/SphK1 axis. The luciferase reporter assays, chromatin immunoprecipitation assays, RNA pull-down, RNA immunoprecipitation, and co-localization assays were performed to elucidate the interactions between LncTUG1, PU.1, and TLR4. Our findings indicated that LncTUG1 overexpression attenuated stress-induced cementocyte mineralization, while blocking the TLR4/SphK1 axis reversed the inhibitory effect of LncTUG1 on stress-induced cementocyte mineralization. The in vivo findings also confirmed the involvement of TLR4/SphK1 signalling in cementocyte mineralization during OTM. Mechanistically, LncTUG1 bound with PU.1 subsequently enhanced TLR4 promotor activity and thus transcriptionally elevated the expression of TLR4. In conclusion, our data revealed a critical role of LncTUG1 in regulating stress-induced cementocyte mineralization via PU.1/TLR4/SphK1 signalling, which might provide further insights for developing novel therapeutic strategies that could protect roots from resorption during OTM.

Recent advances in horizontal alveolar bone regeneration.

Alveolar bone loss is widespread in all age groups and remains a severe hazard to periodontal health. Horizontal alveolar bone loss is the pattern of bone loss more commonly seen in periodontitis. Until now, limited regenerative procedures have been applied to treating horizontal alveolar bone loss in periodontal clinics, making it the least predictable periodontal defect type. This article reviews the literature on recent advances in horizontal alveolar bone regeneration. The biomaterials and clinical and preclinical approaches tested for the regeneration of the horizontal type of alveolar bone are first discussed. Furthermore, current obstacles for horizontal alveolar bone regeneration and future directions in regenerative therapy are presented to provide new ideas for developing an effective multidisciplinary strategy to address the challenge of horizontal alveolar bone loss.

Construction of the Interaction Network of Hub Genes in the Progression of Barrett's Esophagus to Esophageal Adenocarcinoma.

Introduction: Esophageal adenocarcinoma (EAC) is one of the histologic types of esophageal cancer with a poor prognosis. The majority of EAC originate from Barrett's esophagus (BE). There are few studies focusing on the dynamic progression of BE to EAC. Methods: R software was used to analyze differentially expressed genes (DEGs) based on RNA-seq data of 94 normal esophageal squamous epithelial (NE) tissues, 113 BE tissues and 147 EAC tissues. The overlapping genes of DEGs between BE and EAC were analyzed by Venn diagram tool. The hub genes were selected by Cytoscape software based on the protein-protein interaction network of the overlapping genes using STRING database. The functional analysis of hub genes was performed by R software and the protein expression was identified by immunohistochemistry. Results: In the present study, we found a large degree of genetic similarity between BE and EAC, and further identified seven hub genes (including COL1A1, TGFBI, MMP1, COL4A1, NID2, MMP12, CXCL1) which were all progressively upregulated in the progression of NE-BE-EAC. We have preliminarily uncovered the probable molecular mechanisms of these hub genes in disease development and constructed the ceRNA regulatory network of hub genes. More importantly, we explored the possibility of hub genes as biomarkers in the disease progression of NE-BE-EAC. For example, TGFBI can be used as biomarkers to predict the prognosis of EAC patients. COL1A1, NID2 and COL4A1 can be used as biomarkers to predict the response to immune checkpoint blockade (ICB) therapy. We also constructed a disease progression risk model for NE-BE-EAC based on CXCL1, MMP1 and TGFBI. Finally, the results of drug sensitivity analysis based on hub genes showed that drugs such as PI3K inhibitor TGX221, bleomycin, PKC inhibitor Midostaurin, Bcr-Abl inhibitor Dasatinib, HSP90 inhibitor 17-AAG, and Docetaxel may be potential candidates to inhibit the progression of BE to EAC. Conclusion: This study is based on a large number of clinical samples with high credibility, which is useful for revealing the probable carcinogenic mechanism of BE to EAC and developing new clinical treatment strategies.

Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing.

OBJECTIVE: Delayed regeneration of alveolar bone defects because of prolonged inflammation under diabetic conditions remains a challenge for dental rehabilitation in clinic, and effective therapies are required. Cytokines-based immuotherapies might be a potential strategy to regulate inflammation and bone regeneration. Here, we report that local delivery of interleukin-10 (IL-10) by injectable self-assembling peptide (SAP) hydrogel is efficient to promote proinflammatory (M1)-to-anti-inflammatory (M2) phenotype conversion, thereby enhancing bone regeneration in diabetic alveolar bone defects. METHODS: Characteristics of SAP hydrogel were evaluated by morphology, injectable and rheological properties. The loading and release of IL-10 from the SAP hydrogel were evaluated over time in culture. The local inflammatory response and bone repair efficacy of the SAP/IL-10 hydrogel was evaluated in vivo using an alveolar bone defect model of diabetic mice. Finally, the direct effects of M2 macrophage on M1 phenotype and mineralization of MSCs were investigated. RESULTS: In vitro, encapsulated IL-10 could be sustainedly released by SAP hydrogel with preserved bioactivities. In vivo, SAP/IL-10 hydrogel showed significantly higher efficacy to attenuate M1 polarization and proinflammatory factors levels, and enhance expressions of osteogenic factors. As a result, diabetic bone regeneration induced by SAP/IL-10 hydrogel was significantly faster. Mechanistically, M2 macrophages induced by sustained IL-10 delivery might promote diabetic bone regeneration by reprogramming M1 phenotype, suppressing local inflammation and enhancing the osteogenic differentiation of mesenchymal stem cells (MSCs). SIGNIFICANCE: This study highlights that the SAP hydrogel is a promising drug delivery platform for treatment of alveolar bone defects, which might have translational potential in future clinical applications.

Canonical Wnt/ß-catenin signaling has positive effects on osteogenesis, but can have negative effects on cementogenesis.

BACKGROUND: To date, therapeutic approaches for cementum regeneration are limited and outcomes remain unpredictable. A significant barrier to improve therapies for cementum regeneration is that the cementocyte and its intracellular signal transduction mechanisms remain poorly understood. This study aims to elucidate the regulatory mechanism of Wnt pathway in cementogenesis. METHODS: The effects of canonical Wnt signaling were compared in vitro using immortalized murine cementocyte cell line IDG-CM6 and osteocyte cell line IDG-SW3 by quantitative real-time polymerase chain reaction, Western blot, confocal microscopy, alkaline phosphatase (ALP) assay, and Alizarin red S staining. In vivo, histological changes of cementum and bone formation were examined in transgenic mice in which constitutive activation of ß-catenin is driven by Dmp1 promoter. RESULTS: Expression of components of the Wnt/ß-catenin pathway were much greater in the IDG-SW3 cells compared with the IDG-CM6 cells resulting in much lower expression of Sost/sclerostin in the IDG-SW3 cells. In the IDG-CM6 cells, low dose Wnt3a (20 ng/ml) had a modest effect while high dose (200 ng/ml) inhibited runt-related transcription factor 2, osterix, ALP, and osteopontin in contrast to the IDG-SW3 cells where high dose Wnt3a dramatically increased mRNA expression of these same markers. However, high Wnt3a significantly increased mRNA for components of Wnt/ß-catenin signaling pathway in both IDG-CM6 and IDG-SW3 cells. In vivo, constitutive activation of ß-catenin in the Dmp1-lineage cells in mice leads to bone hyperplasia and cementum hypoplasia. CONCLUSION: These findings indicate that Wnt signaling has distinct and different effects on the regulation of long bone as compared with cementum.

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model.

BACKGROUND: Vascular damage, autoimmune abnormalities, and fibrosis are the three pathological features of systemic sclerosis (SSc).However, pulmonary vascular damage is the main factor affecting the progression and prognosis of SSc. The main purpose of this study was to explore the molecular mechanism of Wenyang Huazhuo Tongluo Formula in alleviating pulmonary vascular injury in bleomycin-induced SSc mouse model. METHODS: Masson staining and H&E staining were used to analyze the degree of pulmonary vascular fibrosis and the infiltration of leukocyte cells in lung tissue ofbleomycin-induced SSc mouse models treated with saline (BLM group), Wenyang Huazhuo Tongluo Formula (WYHZTL group) and HIF-1α inhibitor KC7F2 (KC7F2 group). Blood vessel exudation was determined by analyzing the cell number and albumin concentration in bronchoalveolar lavage fluid using a cell counter and ELISA assay, respectively. The degree of vascular injury was assessed by measuring the expression levels of vWF, E-selectin, ICAM-1, VCAM-1, VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells using ELISA and immunofluorescence staining. Finally, the effect of Wenyang Huazhuo Tongluo Formula on the expression of HIF-1α was detected using immunofluorescence staining. RESULTS: Wenyang Huazhuo Tongluo Formula and KC7F2 significantly inhibited bleomycin-induced pulmonary vascular fibrosis and the level of perivascular inflammatory cell infiltration. The number of cells and the concentration of albumin were significantly reduced in the bronchoalveolar lavage fluid of the WYHZTL group and KC7F2 group compared with the BLM group. In addition, treatment with Wenyang Huazhuo Tongluo Formula and KC7F2 significantly downregulated the expression levels of vWF, E-selectin, ICAM-1, VCAM-1 and HIF-1α, but upregulated the expression of VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells, compared with treatment with saline. CONCLUSIONS: This study reveals that Wenyang Huazhuo Tongluo Formula plays a new role in the treatment of SSc by alleviating pulmonary vascular damage. Furthermore, we found that Wenyang Huazhuo Tongluo Formula alleviates pulmonary vascular injury and inhibits HIF-1α expression.

Mechanisms of sphingosine-1-phosphate (S1P) signaling on excessive stress-induced root resorption during orthodontic molar intrusion.

OBJECTIVES: The aim of this study was to investigate cementocyte mechanotransduction during excessive orthodontic intrusive force-induced root resorption and the role of S1P signaling in this process. MATERIALS AND METHODS: Fifty-four 12-week-old male Wistar rats were randomly divided into 3 groups: control group (Control), intrusive stress application group (Stress), and intrusive stress together with S1PR2-specific antagonist injection group (Stress + JTE). A rat molar intrusion model was established on animals in the Stress and the Stress + JTE groups. The animals in the Stress + JTE group received daily intraperitoneal (i.p.) injection of S1PR2 antagonist JTE-013, while the Control and Stress groups received only the vehicle. Histomorphometric, immunohistochemical, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses were performed after euthanizing of the rats. RESULTS: Root resorption was promoted in the Stress group with increased volumes of resorption pits and amounts of molar intrusion compared with the Control group. The expression levels of cementogenic- and cementoclastic-related factors were affected under excessive intrusive force. Immunohistochemical staining and qRT-PCR analysis showed promoted S1P signaling activities during molar intrusion. Western blot analysis indicated decreased nuclear translocation of ß-catenin under excessive intrusive force. Through the administration of JTE-013, S1P signaling activity was suppressed and excessive intrusive force-induced root resorption was reversed. The regulation of S1P signaling could also influence the nuclear translocation of ß-catenin and the expressions of cementogenic- and cementoclastic-related factors. CONCLUSIONS: Root resorption was promoted under excessive orthodontic intrusive force due to the disruption of cementum homeostasis. S1P signaling pathway might play an important role in cementocyte mechanotransduction in this process. CLINICAL RELEVANCE: The S1P signaling might be a promising therapeutic target for novel therapeutic approaches to prevent external root resorption caused by excessive orthodontic intrusive force.

The role of EphB4/ephrinB2 signaling in root repair after orthodontically-induced root resorption.

INTRODUCTION: This study aimed to investigate the effect of EphB4/ephrinB2 signaling on orthodontically-induced root resorption repair and the possible molecular mechanism behind it. METHODS: Seventy-two 6-week-old male Wistar rats were randomly divided into 3 groups: blank control group, physiological regeneration group (PHY), and EphB4 inhibitor local injection group (INH). A root repair model was built on experimental rats of the PHY and INH groups. The animals in the INH groups received a daily periodontal local injection of EphB4 inhibitor NVP-BHG712, whereas the blank control group and PHY groups received only the vehicle. RESULTS: Histologic staining and microcomputed tomography analysis showed that root regeneration was inhibited in the INH group compared with the PHY group with a greater number of osteoclasts. Immunohistochemical staining showed active EphB4/ephrinB2 signaling activities during root regeneration. The cementogenesis-related factors cementum attachment protein, alkaline phosphatase, osteopontin, and runt-related transcription factor 2, and osteoclastic-related factors RANKL and osteoprotegerin were affected by regulated EphB4/ephrinB2 signaling. CONCLUSIONS: These findings demonstrated that the EphB4/ephrinB2 signaling might be a promising therapeutic target for novel therapeutic approaches to reduce orthodontically-induced root resorption through enhancement of cementogenesis.

Intermittent parathyroid hormone improves orthodontic retention via insulin-like growth factor-1.

OBJECTIVES: This study aimed to investigate the effects of intermittent parathyroid hormone (iPTH) on the stability of orthodontic retention and to explore the possible regulatory role of insulin-like growth factor-1 (IGF-1) in this process. METHODS: Forty-eight 6-week-old male Wistar rats were adopted in this study. An orthodontic relapsing model was established to investigate the effects of iPTH on orthodontic retention. In vitro, an immortalized mouse cementoblast cell line OCCM-30 was detected by flow cytometry to study the effects of iPTH on cell proliferation and apoptosis. By application of a specific IGF-1 receptor inhibitor, the role of IGF-1 was also explored. RESULTS: In vivo study found that daily injection of PTH significantly reduced the relapsing distance. Histological staining and ELISA assay showed faster periodontal regeneration during retention period in PTH group with increased RANKL/OPG ratio and greater amount of OCN, ALP, and IGF-1 in gingival cervical fluid (GCF). Cell experiment revealed that iPTH promoted proliferation and suppressed apoptosis of cementoblast. IGF-1 receptor inhibitor significantly restrained the anabolic effect of iPTH on OCCM-30 cells. CONCLUSIONS: These findings suggest that iPTH could improve the stability of tooth movement by promoting periodontal regeneration. IGF-1 is essential in mediating the anabolic effects of iPTH.

Intermittent parathyroid hormone promotes cementogenesis via ephrinB2-EPHB4 forward signaling.

Intermittent parathyroid hormone (PTH) promotes periodontal repair, but the underlying mechanisms remained unclear. Recent studies found that ephrinB2-EPHB4 forward signaling mediated the anabolic effect of PTH in bone homeostasis. Considering the similarities between cementum and bone, we aimed to examine the therapeutic effect of PTH on resorbed roots and explore the role of forward signaling in this process. In vivo experiments showed that intermittent PTH significantly accelerated the regeneration of root resorption and promoted expression of EPHB4 and ephrinB2. When the signaling was blocked, the resorption repair was also delayed. In vitro studies showed that intermittent PTH promoted the expression of EPHB4 and ephrinB2 in OCCM-30 cells. The effects of PTH on the mineralization capacity of OCCM-30 cells was mediated through the ephrinB2-EPHB4 forward signaling. These results support the premise that the anabolic effects of intermittent PTH on the regeneration of root resorption is via the ephrinB2-EPHB4 forward signaling pathway.

Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and ß-catenin.

Periodontitis patients are at risk of alveolar bone loss during orthodontic treatment. The aim of this study was to investigate whether intermittent parathyroid hormone (1-34) treatment (iPTH) could reduce alveolar bone loss during orthodontic tooth movement (OTM) in individuals with periodontitis and the underlying mechanism. A rat model of OTM in the context of periodontitis was established and alveolar bone loss was observed. The control, iPTH and iPTH + stattic groups received injections of vehicle, PTH and vehicle, or PTH and the signal transducer and activator of transcription 3 (STAT3) inhibitor stattic, respectively. iPTH prevented alveolar bone loss by enhancing osteogenesis and suppressing bone resorption in the alveolar bone during OTM in rats with periodontitis. This effect of iPTH was along with STAT3 activation and reduced by a local injection of stattic. iPTH promoted osteoblastic differentiation and might further regulate the Wnt/ß-catenin pathway in a STAT3-dependent manner. The findings of this study suggest that iPTH might reduce alveolar bone loss during OTM in rats with periodontitis through STAT3/ß-catenin crosstalk.

Risk factors for maxillary impacted canine-linked severe lateral incisor root resorption: A cone-beam computed tomography study.

INTRODUCTION: Impacted maxillary canine-linked severe lateral incisor root resorption (SIRRc) is rare, but it greatly influences the survival of the affected teeth. Our study was designed to investigate the risk factors for SIRRc. METHODS: Eighty-two patients with SIRRc and 81 patients with impacted maxillary canines but without SIRRc were included and evaluated by cone-beam computed tomography in software programs by 1 examiner (H.W.). Age, sex, positions, and dental follicles and angular inclinations of impacted canines were measured in this study. Binary logistic regression was used to analyze the risk factors for SIRRc. RESULTS: SIRRc was highly related to sex, vertical and mesiodistal position, dental follicles sizes of canines, and intersection angles in 3 dimensions. The regression analysis showed female sex, dental follicles between 1 mm and 3 mm, mesial third and apical third position, vertical angle smaller than 30°, and the relative angle between 30° and 60° were significant risk factors for SIRRc. CONCLUSIONS: Early diagnosis and treatment for SIRRc are imperative, especially in Asian patients that are female with apically and mesially positioned canines as well as wider dental follicles. Vertical angles and relative angles of impacted canines should also be noticed.

Effects of estrogen on root repair after orthodontically induced root resorption in ovariectomized rats.

INTRODUCTION: This study aimed to investigate the effects of estrogen on root repair after orthodontically induced root resorption. METHODS: Seventy-two 6-week-old female Wistar rats were randomly divided into 3 groups: ovariectomy only (OVX), ovariectomy plus estradiol injection (OVX + E2), and sham operation (control). E2 was administrated to all the experimental animals after the establishment of the root repair model. One-way analysis of variance with the Tukey post-hoc test was used to analyze the experimental results. RESULTS: Micro-computed tomography and hematoxylin and eosin staining showed that the total volumes of resorption lacunae were significantly smaller in the control and OVX + E2 groups than those in the OVX group. Alkaline phosphatase and tartrate-resistant acid phosphatase stainings suggested that the cementoblastic activities and the amount of new cementum formation were inhibited while the activities of osteoclasts were obvious in the OVX group. The immunohistochemistry stainings revealed that the osteoprotegerin to receptor activator of nuclear factor-кB ligand ratio and the phosphorylated extracellular signal-regulated kinases to extracellular signal-regulated kinases ratio of the control and OVX + E2 groups were significantly greater than those of the OVX group. CONCLUSIONS: These findings demonstrated that estrogen administration might be a solution to reduce orthodontically induced root resorption through the activation of extracellular signal-regulated kinase-1/2 pathway and enhancement of cementogenesis.

The role of sphingosine-1-phosphate signaling pathway in cementocyte mechanotransduction.

Iatrogenic external root resorption can become a serious pathological condition with clinical tooth movement. Little is known regarding how cementum responds to mechanical loading in contrast to bone, especially under compressive stress. In the field of bone biology, several studies have established the contribution of sphingosine-1-phosphate (S1P) signaling in bone remodeling, mechanical transduction and homeostasis. As osteocytes and cementocytes share similar morphological and functional characteristics, this study aimed to investigate the mechanotransduction ability of cementocytes and to explore the contribution of S1P signaling under compressive stress induced mechanotransduction. We found that compressive stress inhibited major S1P signaling and promoted the expression of anabolic factors in IDG-CM6 cells, a novel immortalized murine cementocyte cell line. By inhibiting S1P signaling, we verified that S1P signaling played a vital role in regulating the expression of the mechanotransduction factors prostaglandin E2 (PGE2) and ß-catenin, as well as factors responsible for cementogenesis and cementoclastogenesis in IDG-CM6 cells. These results support the hypothesis that cementocytes act as key mechanically responsive cells in cementum, responding to compressive stress and directing local cementum metabolism.

Gender differences in the association of periodontitis and type 2 diabetes.

AIMS: THE OBJECTIVE WAS TO INVESTIGATE IF GENDER DIFFERENCES EXIST IN THE ASSOCIATIONS BETWEEN PERIODONTITIS AND TYPE 2 DIABETES. DISPROPORTIONATE DISPARITIES BY GENDER WERE FOUND TO EXIST IN RATES OF BOTH PERIODONTITIS AND DIABETES WITH RESPECT TO DEMOGRAPHICS AND BEHAVIOURAL PREDICTORS THAT CANNOT BE EXPLAINED SOLELY BY THE WELL-ESTABLISHED ASSOCIATION BETWEEN THESE TWO DISEASES. MATERIALS AND METHODS: MULTIPLE DATASETS WERE EXTRACTED FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES) 2009-2014, WHICH USED A STRATIFIED MULTISTAGE PROBABILITY SAMPLING TO OBTAIN SAMPLES FROM ALL CIVILIAN NON-INSTITUTIONALISED PEOPLE IN THE USA. BIVARIATE RELATIONSHIPS BETWEEN EACH EXPLANATORY VARIABLE AND PERIODONTITIS LEVEL WERE ASSESSED WITH ODDS RATIOS (OR) AND THEIR 95% CONFIDENCE INTERVALS (CI). A SET OF WEIGHTED LOGISTIC REGRESSION MODELS WAS USED TO INVESTIGATE THE ASSOCIATION DIFFERENTIATIONS BETWEEN PERIODONTITIS AND DIABETES BY GENDER. C-STATISTICS MEASURED THE GOODNESS-OF-FIT OF WEIGHTED LOGISTIC REGRESSION MODELS. RESULTS: THE PREVALENCE OF MODERATE-SEVERE PERIODONTITIS WAS 36.39% AND 22.71% AMONG PARTICIPANTS WITH TYPE 2 DIABETES AND WITHOUT DIABETES, RESPECTIVELY. TYPE 2 DIABETES WAS SIGNIFICANTLY ASSOCIATED WITH MODERATE-SEVERE PERIODONTITIS OR (OR = 1.47, 95% CI: 1.18-1.82) AMONG MALES EVEN AFTER ADJUSTING FOR DEMOGRAPHICS, SOCIOECONOMIC STATUS AND ORAL HEALTH BEHAVIOURS. THE AFOREMENTIONED RELATIONSHIP WAS NOT FOUND IN FEMALES. FURTHERMORE, DIFFERENT RELATIONSHIPS OF MODERATE-SEVERE PERIODONTITIS WITH BODY MASS INDEX AND THE USE OF MOUTHWASH WERE FOUND BETWEEN THE MALES AND FEMALES. CONCLUSIONS: THE CURRENT FINDINGS SUGGEST THAT IMPORTANT IMPROVEMENTS IN THE DEVELOPMENT OF GENDER-SPECIFIC STRATEGIES IN PREVENTION, SUCH AS ORAL HOME-CARE, TO REDUCE THE HIGH PREVALENCE OF PERIODONTAL DISEASE AND MAINTAIN GOOD ORAL HEALTH ARE VITAL, AND ARE ESPECIALLY IMPORTANT FOR MALE DIABETIC PATIENTS AND THOSE WHO ARE AT HIGH RISK OF DEVELOPING DIABETES, SUCH AS THOSE WHO ARE OBESE.

Insights into the roles of lncRNAs in skeletal and dental diseases.

Long noncoding RNAs (lncRNAs) are a class of non-protein-coding transcripts with the length longer than 200 nucleotides. Growing evidence suggests that lncRNAs, which were initially thought to be merely transcriptional "noise", participate in a wide repertoire of biological processes. It has been well established that lncRNAs not only play important roles in genomic regulation, transcription, posttranscriptional processes but are also implicated in the pathogenesis of human diseases including cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. However, the pathological role of lncRNAs in skeletal and dental diseases is just beginning to be uncovered. In the present review, we outline the current understanding of the established functions and underlying mechanisms of lncRNAs in various cellular processes. Furthermore, we discuss new findings on the role of lncRNAs in osteoblastogenesis and osteoclastogenesis as well as their involvement in skeletal and dental diseases. This review intends to provide a general framework for the actions of lncRNAs and highlight the emerging evidence for the functions of lncRNAs in skeletal and dental diseases.

Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading.

As the ß-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of ß-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of ß-catenin against the effects of stress in males and partial protection against unloading in females.