Predicting obstructive sleep apnea hypopnea syndrome using three-dimensional optical devices: A systematic review.

Purpose: As a global health concern, the diagnosis of obstructive sleep apnea hypopnea syndrome (OSAHS), characterized by partial reductions and complete pauses in ventilation, has garnered significant scientific and public attention. With the advancement of digital technology, the utilization of three-dimensional (3D) optical devices demonstrates unparalleled potential in diagnosing OSAHS. This study aimed to review the current literature to assess the accuracy of 3D optical devices in identifying the prevalence and severity of OSAHS. Methods: A systematic literature search was conducted in the Web of Science, Scopus, PubMed/MEDLINE, and Cochrane Library databases for English studies published up to April 2024. Peer-reviewed researches assessing the diagnostic utility of 3D optical devices for OSAHS were included. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) guideline was employed to appraise the risk of bias. Results: The search yielded 3216 results, with 10 articles meeting the inclusion criteria for this study. Selected studies utilized structured light scanners, stereophotogrammetry, and red, green, blue-depth (RGB-D) cameras. Stereophotogrammetry-based 3D optical devices exhibited promising potential in OSAHS prediction. Conclusions: The utilization of 3D optical devices holds considerable promise for OSAHS diagnosis, offering potential improvements in accuracy, cost reduction, and time efficiency. However, further clinical data are essential to assist clinicians in the early detection of OSAHS using 3D optical devices.

Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium.

AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

Cystathionine γ-lyase contributes to exacerbation of periodontal destruction in experimental periodontitis under hyperglycemia.

BACKGROUND: Diabetes is one of the major inflammatory comorbidities of periodontitis via 2-way interactions. Cystathionine γ-lyase (CTH) is a pivotal endogenous enzyme synthesizing hydrogen sulfide (H2S), and CTH/H2S is crucially implicated in modulating inflammation in various diseases. This study aimed to explore the potential role of CTH in experimental periodontitis under a hyperglycemic condition. METHODS: CTH-silenced and normal human periodontal ligament cells (hPDLCs) were cultured in a high glucose and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) condition. The effects of CTH on hPDLCs were assessed by Cell Counting Kit 8 (CCK8), real-time quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The model of experimental periodontitis under hyperglycemia was established on both Cth-/- and wild-type (WT) mice, and the extent of periodontal destruction was assessed by micro-CT, histology, RNA-Seq, Western blot, tartrate-resistant acid phosphatase (TRAP) staining and immunostaining. RESULTS: CTH mRNA expression increased in hPDLCs in response to increasing concentration of P.g-LPS stimulation in a high glucose medium. With reference to WT mice, Cth-/- mice with experimental periodontitis under hyperglycemia exhibited reduced bone loss, decreased leukocyte infiltration and hindered osteoclast formation, along with reduced expression of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in periodontal tissue. RNA-seq-enriched altered NF-κB pathway signaling in healthy murine gingiva with experimental periodontitis mice under hyperglycemia. Accordingly, phosphorylation of p65 (P-p65) was alleviated in CTH-silenced hPDLCs, leading to decreased expression of IL6 and TNF. CTH knockdown inhibited activation of nuclear factor kappa-B (NF-κB) pathway and decreased production of proinflammatory cytokines under high glucose and P.g-LPS treatment. CONCLUSION: The present findings suggest the potential of CTH as a therapeutic target for tackling periodontitis in diabetic patients.

Association among physical activity, anxiety and oral health status in Chinese university students: A cross-sectional study.

Background: Evidence is limited regarding the relationship among physical activity, anxiety, and oral health in Chinese university students. This cross-sectional investigation aimed to assess the potential relationship between physical activity, anxiety, and oral health conditions among university students in China. Methods: An online questionnaire measuring physical activity, anxiety status, and oral health condition was completed by 1604 university students. The International Physical Activity Questionnaire Short Form (IPAQ-SF) and Generalized Anxiety Disorder-7 (GAD-7) were selected to evaluate physical activity and anxiety, respectively. Oral health condition was assessed through several self-reported variables, including self-reported toothache, gingival bleeding, frequency of tooth brushing, and use of dental floss. Multivariate logistic regression was performed to analyze the underlying relationship between outcome variables. The control variables included age, height, weight, gender, whether only one-child, education level, parental education level, smoking status, drinking habits, and length of sleep. Path analysis was conducted to disentangle the association between physical activity, anxiety, and oral health conditions. Results: Among 1604 university students, 666 (41.5 %) were males and 938 (58.5 %) were females, with an average of 21.9 ± 2.8 years. Only 833 (51.9 %) reported sufficient physical activity, while 684 (42.6 %) of the subjects displayed varying degrees of anxiety. Self-reported gingival bleeding was associated with insufficient physical activity (OR = 1.25; 95%CI: 1.02-1.55), anxiety (OR = 0.45; 95%CI: 0.27-0.74), frequency of tooth brushing (OR = 0.75; 95%CI: 0.60-0.95) and use of dental floss (OR = 0.75; 95%CI: 0.59-0.96), while toothache was not directly influenced by the physical activity and anxiety among university students. Anxiety markedly mediated the relationship between physical activity and oral health conditions. Conclusions: Anxiety was considered a factor associated with the level of physical activity, tooth brushing habits, and self-reported gingival bleeding among university students. Further investigations are required to elucidate whether oral health conditions could be enhanced through the improvement of anxiety and physical activity.

A bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy.

Osteoporosis (OP), which largely increases the risk of fractures, is the most common chronic degenerative orthopedic disease in the elderly due to the imbalance of bone homeostasis. Alpha-ketoglutaric acid (AKG), an endogenous metabolic intermediate involved in osteogenesis, plays critical roles in osteogenic differentiation and mineralization and the inhibition of osteoclastogenic differentiation. However, the low bioavailability and poor bone-targeting efficiency of AKG seriously limit its efficacy in OP treatment. In this work, a bone-targeting, near-infrared emissive lanthanide luminescence nanocarrier loaded with AKG (ß-NaYF4:7%Yb, 60%Nd@NaLuF4@mSiO2-EDTA-AKG, abbreviated as LMEK) is developed for the enhancement of AKG efficacy in OP therapy. By utilizing the NIR-II luminescence (>1000 nm) of LMEK, whole-body bone imaging with high spatial resolution is achieved to confirm the bone enrichment of AKG noninvasively in vivo. The results reveal that LMEK exhibits a remarkable OP therapeutic effect in improving the osseointegration of the surrounding bone in the ovariectomized OP mice models, which is validated by the enhanced inhibition of osteoclast through hypoxia-inducible factor-1α suppression and promotion of osteogenic differentiation in osteoblast. Notably, the dose of AKG in LMEK can be reduced to only 0.2 % of the dose when pure AKG is used in therapy, which dramatically improves the bioavailability of AKG and mitigates the metabolism burden. This work provides a strategy to conquer the low utilization of AKG in OP therapy, which not only overcomes the challenges in AKG efficacy for OP treatment but also offers insights into the development and application of other potential drugs for skeletal diseases. STATEMENT OF SIGNIFICANCE: Alpha-ketoglutarate (AKG) is an intermediate within the Krebs cycle, participating in diverse metabolic and cellular processes, showing potential for osteoporosis (OP) therapy. However, AKG's limited bioavailability and inefficient bone-targeting hinder its effectiveness in treating OP. Herein, a near-infrared emissive nanocarrier is developed that precisely targets bones and delivers AKG, bolstering its effectiveness in OP therapy. Thanks to this efficient bone-targeting delivery, the AKG dosage is reduced to 0.2 % of the conventional treatment level. This marks the first utilization of a bone-targeting nanocarrier to amplify AKG's bioavailability and OP therapy efficacy. Furthermore, the mechanism of AKG-loaded nanocarrier regulating the biological behavior of osteoclasts and osteoblasts mediated is tentatively explored.

Improvement of parents' oral health knowledge by a school-based oral health promotion for parents of preschool children: a prospective observational study.

BACKGROUND: Parents of preschool children have inadequate oral health knowledge in Hong Kong. Parents play a critical role in preschool children's dietary patterns and oral health behaviors. A school-based oral health promotion (OHP) for parents of preschoolers was developed and investigated. OBJECTIVES: The objective of this study was to evaluate effects of the school-based OHP for parents of preschool children on parents' oral health knowledge and preschool children's early childhood caries (ECC). MATERIALS AND METHODS: This was a quasi-experimental study. Parents of preschool children were divided into the intervention group (IG) and the control group (CG) according to their own selection. Parents in the IG participated in a structured school-based OHP workshop, while those in the CG did not attend the OHP workshop. Parents in both groups were invited to complete a questionnaire assessing their oral health knowledge before (T0), one month after (T1), and twelve months after (T2) the OHP workshop. Preschool children's caries was examined via dmft score at T0 and T2. RESULTS: Parents' oral health knowledge was negatively correlated with preschool children's dmft scores (R = -0.200, P < 0.001). Oral health knowledge was significantly improved in IG (P < 0.001) but not in CG (P = 0.392) at T1. Both groups experienced a significant improvement in oral health knowledge from T0 to T2 (P < 0.001). Parents' oral health knowledge in the IG was significantly higher compared to the CG at T1 (P < 0.001), but difference in the scores at T2 between the two groups showed no significant difference (P = 0.727). No significant difference was found in changes in children's dmft score from T0 to T2 between the IG and CG (p = 0.545). CONCLUSION: Preschool children's high ECC is associated with the limited oral health knowledge of their parents. The school-based OHP workshop for parents increased parents' oral health knowledge within one month. This positive effect was maintained for twelve months and can be extended to a larger scale in the school setting.

Human bone marrow mesenchymal stem cell-derived extracellular vesicles restore Th17/Treg homeostasis in periodontitis via miR-1246.

T-cell-mediated immunity is crucial in the immunopathology of periodontitis. The restoration of the homeostasis between the T helper cell 17 (Th17) and regulatory T cell (Treg) subsets by extracellular vesicles (EVs) obtained from human bone marrow stem cells (hBMSCs) promotes new bone formation and suppresses inflammation. Uncovering the functions of hBMSC-derived EVs in the immune microenvironment of periodontal tissue and their underlying regulatory mechanisms may shed new light on developing potential cell-free immunotherapies for periodontal regeneration. Here, we reported that the Th17/Treg ratio elevated in peripheral blood from periodontitis patients. Furthermore, we found that hBMSC-derived EVs could reduce the Th17/Treg ratio in CD4+ T cells from periodontitis patients in vitro and ameliorate conditions of experimental periodontitis in mice. Additionally, by investigating the differentially expressed miRNAs and target genes in EVs from hBMSCs stimulated with Porphyromonas gingivalis LPS using miRNA sequencing, we found that EV-miR-1246 is highly effective at downregulating the ratio of Th17/Treg in vitro. Mechanistically, EV-miR-1246 suppressed expression of its potential target angiotensin-converting enzyme 2 (ACE2) and increased the p-Yes-associated protein (YAP)1/YAP1 ratio in CD4+ T cells. Our results indicated that hBMSC-derived EVs improve periodontitis via miR-1246, consequently downregulating Th17/Treg ratio, and represented a promising therapeutic target for precision treatment in periodontitis.

Identification and assessment of differentially expressed necroptosis long non-coding RNAs associated with periodontitis in human.

BACKGROUND: Periodontitis is the most common oral disease and is closely related to immune infiltration in the periodontal microenvironment and its poor prognosis is related to the complex immune response. The progression of periodontitis is closely related to necroptosis, but there is still no systematic study of long non-coding RNA (lncRNA) associated with necroptosis for diagnosis and treatment of periodontitis. MATERIAL AND METHODS: Transcriptome data and clinical data of periodontitis and healthy populations were obtained from the Gene Expression Omnibus (GEO) database, and necroptosis-related genes were obtained from previously published literature. FactoMineR package in R was used to perform principal component analysis (PCA) for obtaining the necroptosis-related lncRNAs. The core necroptosis-related lncRNAs were screened by the Linear Models for Microarray Data (limma) package in R, PCA principal component analysis and lasso algorithm. These lncRNAs were then used to construct a classifier for periodontitis with logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the model. The CIBERSORT method and ssGSEA algorithm were used to estimate the immune infiltration and immune pathway activation of periodontitis. Spearman's correlation analysis was used to further verify the correlation between core genes and periodontitis immune microenvironment. The expression level of core genes in human periodontal ligament cells (hPDLCs) was detected by RT-qPCR. RESULTS: A total of 10 core necroptosis-related lncRNAs (10-lncRNAs) were identified, including EPB41L4A-AS1, FAM30A, LINC01004, MALAT1, MIAT, OSER1-DT, PCOLCE-AS1, RNF144A-AS1, CARMN, and LINC00582. The classifier for periodontitis was successfully constructed. The Area Under the Curve (AUC) was 0.952, which suggested that the model had good predictive performance. The correlation analysis of 10-lncRNAs and periodontitis immune microenvironment showed that 10-lncRNAs had an impact on the immune infiltration of periodontitis. Notably, the RT-qPCR results showed that the expression level of the 10-lncRNAs obtained was consistent with the chip analysis results. CONCLUSIONS: The 10-lncRNAs identified from the GEO dataset had a significant impact on the immune infiltration of periodontitis and the classifier based on 10-lncRNAs had good detection efficiency for periodontitis, which provided a new target for diagnosis and treatment of periodontitis.

Black phosphorus thermosensitive hydrogels loaded with bone marrow mesenchymal stem cell-derived exosomes synergistically promote bone tissue defect repair.

The osteogenic function of mesenchymal stem cells (MSCs) is mainly attributed to the paracrine effect of extracellular vesicles. MSC-derived exosomes are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials, and have emerged as cell-free regenerative medicine in recent years. In this study, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were loaded with photothermal material layered black phosphorus (BP) modified poly(N-isopropylacrylamide) (PNIPAAm) thermosensitive hydrogels to explore their effects on bone defect repair. In vitro, it was confirmed that the local high heat of nano-BP irradiated using a near-infrared (NIR) laser could trigger the reversible cascade reaction of hydrogels, and that the mechanical contraction of hydrogels led to the controllable release of a large number of exosomes along with the release of water molecules. Furthermore, in vitro investigations demonstrated that BP hydrogels loaded with BMSC-derived exosomes had favourable biocompatibility and could promote the proliferation and osteogenic differentiation of MSCs. Experiments conducted in vivo confirmed that this system significantly promoted bone regeneration. Therefore, the results of our study indicated that the nanoplatform based on BP thermosensitive hydrogels could provide a new clinical treatment strategy for controlled release and on-demand drug delivery, while the cell-free system composed of BMSC-derived exosomes had great application potential in bone tissue repair with the synergism of BP.

Weakening of M1 macrophage and bone resorption in periodontitis cystathionine γ-lyase-deficient mice.

OBJECTIVES: Cystathionine-γ-lyase (CTH) has been proved to involve in inflammation and bone remolding, implying its potential role in the progression of periodontitis. This study was aimed to investigate the function of CTH and its relation to the macrophage polarization in periodontitis. MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Cth knockout (Cth-/- ) mice were stimulated with lipopolysaccharide (LPS) in vitro and pro-inflammatory cytokines were analyzed by qRT-PCR. Ligature-induced periodontitis was established on WT and Cth-/- mice. Histological analysis, tartrate-resistant acid phosphatase staining, immunostaining, and Western blot were performed to analyze the periodontium destruction and M1 macrophage polarization. RESULTS: Cth expression in BMDMs was upregulated upon increasing LPS stimulation. Deletion of Cth suppressed BMDMs inflammatory response with decreased Il1b, Il6, and Tnf mRNA. Cth-/- mice with periodontitis showed attenuated bone loss and impaired osteoclast differentiation compared with WT. Moreover, Cth knockout hindered M1 macrophage polarization, reduced the expression of IL-1ß, IL-6, and TNF-α in periodontally diseased tissue. CONCLUSION: This study demonstrated that CTH played an important role in regulating the inflammatory responses and periodontitis tissue destruction. Importantly, Cth knockout suppressed M1 macrophages polarization in periodontitis.

3-Dimensional simulations and student learning in orthodontic education.

INTRODUCTION: The electronic dental model (e-model) is an example of a digital 3-dimensional technology to support inquiry-based learning in undergraduate dental education. As student perceptions of and engagement with e-models vary, it is uncertain whether these perceptions have implications for their learning processes and outcomes. MATERIALS AND METHODS: Third-year dental students (N = 40) completed a questionnaire to identify their perceptions of and preferences for model modalities. They were divided into three groups based on their preference: Preferring plaster models (Group 1); Preferring e-models (Group 2); No preference (Group 3). Students from three groups (N = 9) attended a hands-on digital occlusion evaluation workshop, and then completed a case-based diagnostic evaluation test using digital occlusion evaluation software. Camtasia Studio™ recorded real-time and on-screen data of the number of mouse-clicks and time spent. RESULTS: Students reported positive feedbacks on the use of e-models, and 72.5% of the students preferred combination use of e-models and plaster models. After attending the hands-on digital dental occlusion evaluation workshop, Group 2 scored higher on the diagnostic evaluation test (p < .05) and registered more mouse-clicks than Group 1 when evaluating the arch symmetry (p < .05). Group 2 registered fewer mouse-clicks than Group 3 during tooth size measurement (p < .05). There was no significant difference regarding the time used to answer the knowledge questions amongst the three groups. CONCLUSION: Undergraduate dental students indicated a generally high acceptance of e-models for their learning in orthodontics, and more prefer a blended approach. Students preferring e-models presented higher performance outcomes, which supports cognitive load theory regarding prior exposure to simulation-based environments.

Circadian transcription factor Dbp promotes rat calvarial osteoprogenitors osteogenic differentiation through Kiss1/GnRH/E2 signaling pathway loop.

To determine the mechanism by which D-site-binding protein (Dbp) regulates rat calvarial osteoprogenitors (OPCs) osteogenic differentiation. α-Smooth muscle actin (α-SMA) + rat calvarial OPCs were extracted and purified using immunomagnetic beads. Cells were transduced with Dbp-lentivirus and divided into Dbp knockdown, Dbp overexpression and vehicle groups. After osteogenic induction for 21 days, Alizarin red staining and alkaline phosphatase (ALP) activity were examined. Expression levels of Runx2, Ocn, Osterix, Bmp4, Kiss1, and GnRH were determined using a quantitative real-time polymerase chain reaction. The observed changes in Kisspeptin, GnRH, ERα, and Runx2 were further validated via Western blot analysis. Furthermore, E2 and GnRH secretion levels were detected via an enzyme-linked immunosorbent assay (ELISA). Chromatin immunoprecipitation (ChIP) and luciferase assay were used to assess the effects of Dbp on the Kiss1 gene promoter. The coexpression of Dbp and Kisspeptin or GnRH was also evaluated via immunofluorescence. Following osteogenic induction, Dbp overexpression significantly increased calcium nodule formation and ALP activity, as well as Runx2, Ocn, Osterix, Bmp4, Kiss1, and GnRH messenger RNA expression, while Dbp knockdown presented the opposite results. Western blot analysis and ELISA results showed that Dbp significantly promotes Runx2, E2/ERα, Kisspeptin, and GnRH expression. These findings were confirmed by the ChIP assay, which indicated that the estrogen receptor promotes Kisspeptin expression after binding to the Kiss1 gene promoter, which is regulated by Dbp. Immunofluorescence assay showed that Dbp coexpression with Kisspeptin or GnRH varied depending on Dbp expression levels. Collectively, the circadian transcription factor Dbp promotes α-SMA + rat calvarial OPCs osteoblastic differentiation through Kiss1/GnRH/E2 signaling pathway loop.

IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes.

Bone remodeling is a strictly regulated dynamic process that cycles between bone formation and resorption, and interleukin-17 (IL-17) critically orchestrates the activation and differentiation of both osteoblasts and osteoclasts. Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that influences their differentiation into bone precursors, while the roles of osteocytes in regulating the osteogenic differentiation of MSCs remain unclear. This study investigated the specific roles of IL-17 signaling cascades and osteocyte-specific pathways in the osteogenesis of MSCs. Using a transwell coculture (CC) system, we explored the effects of osteocytes and osteoblasts on the osteogenesis of MSCs with and without IL-17 supplementation. A polycaprolactone (PCL) three-dimensional (3D) culture model was used to evaluate their osteogenic potential in the presence of osteocytes and IL-17. Notably, IL-17 induced osteogenesis in MSCs, which could be attenuated by blocking IL-17 receptor A. The osteogenic differentiation of MSCs promoted by IL-17 was further enhanced by CC with osteocytes. Moreover, proinflammatory cytokines IL-6 and IL-1ß played an important role in IL-17-dependent differentiation, via the phosphorylation of AKT, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase 1/2 signaling pathways in the MSC niche. The present study confirms a synergistic effect of osteocytes and IL-17 in the production of biochemical signals to stimulate the osteogenic differentiation of MSCs, which could be further promoted in the PCL 3D-scaffold. These findings provide important insight into the mechanisms of MSCs activation and osteogenic differentiation within the native stem cell niche, and suggest a possible role of IL-17 in bone tissue engineering.

Digital Models as an Alternative to Plaster Casts in Assessment of Orthodontic Treatment Outcomes.

OBJECTIVE: This study aimed to compare the use of digital models and plaster casts in assessing the improvement in occlusion following orthodontic treatment. MATERIALS AND METHODS: Digital models and plaster casts of 39 consecutive patients at pre- and posttreatment stages were obtained and assessed using the Peer Assessment Rating (PAR) index and the Index of Complexity and Treatment Need (ICON). PAR and ICON scores were compared at individual and group levels. Categorization of improvement level was compared using Kappa (κ) statistics. RESULTS: There was no significant difference in neither PAR scores (p > 0.05) nor ICON scores (p > 0.05) between digital and plaster cast assessments. The Intraclass Correlation Coefficient (ICC) values for changes in PAR and ICON scores were excellent (ICC > 0.80). Agreement of ratings of occlusal improvement level between digital and plaster model assessments was 0.83 (κ) for PAR and 0.59 (κ) for ICON, respectively. CONCLUSION: The study supported the use of digital models as an alternative to plaster casts when assessing changes in occlusion at the 'individual patient' level using ICON or PAR. However, it could not fully support digital models as an alternate to plaster casts at 'the group level' (as in the case of clinical audit/research).

Pivotal Roles of Interleukin-17 as the Epicenter of Bone Loss Diseases.

Bone remodelling is a strictly regulated dynamic process between bone resorption and bone formation. Many factors are involved in the process and affect the dynamic balance. Inflammation-mediated bone loss is a major feature of various bone diseases, including periodontitis, rheumatoid arthritis (RA) and spondyloarthritis (SpA). Interleukin-17 (IL-17) plays an important role in inflammatory bone disease and could be an attractive therapeutic target. This review focuses on the osteoclastic effects of IL-17 in different cell types and summarizes the current knowledge of IL-17 signalling pathways. Typical IL-17-mediated bone destruction disorders are examined. The review also provides an overview of possible strategies for therapeutic intervention for inflammatory loss of bone targeting IL-17.

Shear stress inhibits IL-17A-mediated induction of osteoclastogenesis via osteocyte pathways.

Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells. Additionally, shear stress upregulated osteoprotegerin expression in osteocytes, downregulated the effect of IL-17A on RANKL and TNF-α expression, and attenuated IL-17A-activated osteoclastic differentiation in the co-culture system of MLO-Y4 and BMM cells. Furthermore, we explored the signaling pathways that potentially mediate these effects in osteocytes, and found that the extracellular signal-regulated kinase (ERK)1/2 and signal transducer and activator of transcription (STAT3) pathways were suppressed by IL-17A but induced by fluid flow. EphA2 signaling enhances osteoclastogenesis in osteocytes, and the intercellular reversed EphA2-ephrinA2 signaling from osteocytes to BMM play an important role in IL-17A-dependent osteoclastic differentiation. EphB4 signaling inhibits osteoclastogenesis in osteocytes, and the intercellular reversed EphB4-ephrinB2 signaling from osteocytes to BMM could inhibit IL-17A-dependent osteoclastic differentiation. The current findings suggest that IL-17A as a promoter of bone resorption and fluid shear stress critically regulate bone remodeling via osteocyte-specific signaling pathways. IL-17 modulation-based approaches may be developed as a novel therapeutic strategy for enhancing bone remodeling efficiency and stability.

Change of mandibular position during two-phase orthodontic treatment of skeletal class II in the Chinese population.

The aim of this study was to evaluate the change in mandibular position during a two-phase orthodontic treatment of skeletal Class II malocclusion. Thirty consecutively treated Chinese male adolescents who had undergone two-phase treatment with Herbst appliance and fixed appliance and fulfilled the specific selection criteria were sampled. Cephalograms taken at T0 (before treatment), T1 (at the end of functional appliance treatment), and T2 (at the end of fixed appliance treatment) were analyzed. The change in sagittal positioning of the mandible was 6.8 ± 3.44 mm in phase I (T0-T1), 0.4 ± 2.79 mm in phase II (T1-T2), and 7.2 ± 4.61 mm in total. The mandible came forward in 100% of the patients at T1. In phase II, it came forward in one-third (positive group) remained unchanged in one-third (stable group) and went backward in one-third (negative group) of the patients. At T2, it came forward twice as much in the positive group compared to the negative group. Mandibular length was significantly increased in 100% of the patients in both phases. In conclusion, during the treatment with functional appliance, the mandibular prognathism increases in all patients, whereas during the treatment with fixed appliance there is no significant change in mandibular prognathism.

The relationship between the cranial base and jaw base in a Chinese population.

INTRODUCTION: The cranial base plays an important role in determining how the mandible and maxilla relate to each other. This study assessed the relationship between the cranial base and jaw base in a Chinese population. METHODS: This study involved 83 subjects (male: 27; female: 56; age: 18.4±4.2 SD years) from Hong Kong, who were classified into 3 sagittal discrepancy groups on the basis of their ANB angle. A cephalometric analysis of the angular and linear measurements of their cranial and jaw bases was carried out. The morphological characteristics of the cranial and jaw bases in the three groups were compared and assessments were made as to whether a relationship existed between the cranial base and the jaw base discrepancy. RESULTS: Significant differences were found in the cranial base angles of the three groups. Skeletal Class II cases presented with a larger NSBa, whereas skeletal Class III cases presented with a smaller NSBa (P<0.001). In the linear measurement, skeletal Class III cases presented with a shorter NBa than skeletal Class I and II cases (P<0.01). There was a correlation between the cranial base angle NSBa and the SNB for the whole sample, (r=-0.523, P<0.001). Furthermore, correlations between SBaFH and Wits (r=-0.594, P<0.001) and SBaFH and maxillary length (r=-0.616, P<0.001) were more obvious in the skeletal Class III cases. CONCLUSIONS: The cranial base appears to have a certain correlation with the jaw base relationship in a southern Chinese population. The correlation between cranial base and jaw base tends to be closer in skeletal Class III cases.

Effect of hydrogen sulphide on the expression of osteoprotegerin and receptor activator of NF-κB ligand in human periodontal ligament cells induced by tension-force stimulation.

OBJECTIVE: Hydrogen sulphide (H2S) is an endogenous gaseous signalling molecule, the generation rate of which is affected by mechanical force in cells. Recently, it was reported that mechanical force plays an important role in some pathways such as osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) in human periodontal ligament cells (hPDLCs). Here, we investigated whether H2S played a regulatory role within the periodontal remodelling process by addressing the expression level of OPG/RANKL in hPDLCs. DESIGN: hPDLCs were first applied with tension force for 0-120min to select the optimal time for force application. These cells were treated with H2S for 24h followed by stimulation with tension-force application. Cell proliferation and apoptosis were assessed by the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry analysis. For OPG, RANKL and cystathionine-γ-lyase (CSE), real-time polymerase chain reaction (PCR) was used to analyse the messenger RNA (mRNA) expression; enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of OPG and soluble RANKL (sRANKL). RESULTS: Tension force promoted the mRNA expression of CSE and the optimal application time was 60min. The expression of OPG was increased in a concentration-dependent manner by H2S treatment. Importantly, the relative OPG/RANKL expression ratio was significantly increased upon induction by H2S, an effect that was enhanced by tension-force application. CONCLUSIONS: H2S could promote osteogenic differentiation by regulating the relative OPG/RANKL expression ratio of hPDLCs, which is enhanced by tension force. These findings may be valuable for understanding the mechanism of H2S in the periodontal remodelling, especially in the process of tooth movement.