Influence of feeding a soft diet on proteoglycan expression in rat temporomandibular joint discs.

OBJECTIVES: Extracellular matrix components play a significant role in maintaining tissue integrity and pathological processes of the temporomandibular joint (TMJ). This study aimed to evaluate the influence of a soft diet on the mRNA expression of proteoglycans and glycosaminoglycans (GAGs) linked to proteoglycan core proteins in rat TMJ discs. METHODS: Thirty 4-week-old male Wistar rats were assigned to one of two groups: a control group fed a regular pellet diet and a soft diet group fed a powdered diet for 4 weeks. The mRNA expression levels of 12 proteoglycans in TMJ discs were evaluated using real-time polymerase chain reaction (PCR). In addition, histomorphometric and biochemical analyses were performed to evaluate the thickness and deoxyribonucleic acid (DNA), GAG, and water content of the TMJ discs. RESULTS: The TMJ disc thickness in the anterior, intermediate, and posterior bands decreased significantly in the soft diet group. The GAG content decreased significantly in the soft-diet group, whereas no significant differences in DNA content or water content ratio were observed between the groups. Real-time PCR indicated that the expression levels of aggrecan, versican, biglycan, decorin, fibromodulin, lumican, and chondroadherin decreased in the soft diet group. The expression levels of all versican isoforms decreased in the soft diet group. CONCLUSIONS: These results indicate that the biomechanical environment of the TMJ caused by a soft diet is closely related to the expression of proteoglycans in TMJ discs, which may eventually increase the fragility of the TMJ discs.

Three-Dimensional Evaluation of Treatment Effects and Post-Treatment Stability of Maxillary Molar Intrusion Using Temporary Anchorage Devices in Open Bite Malocclusion.

Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.

Three-dimensional morphologic analysis of the maxillary alveolar bone after anterior tooth retraction with temporary anchorage devices.

OBJECTIVES: To investigate three-dimensional (3D) morphologic changes in the alveolar bone around the maxillary central incisors of patients who underwent premolar extraction and subsequent anterior tooth retraction using temporary anchorage devices (TADs). MATERIALS AND METHODS: The subjects consisted of 16 patients with bimaxillary protrusion. The maxillary anterior teeth were retracted using sliding or loop mechanics and TADs for anchorage reinforcement. Cephalograms and computed tomography scans taken pretreatment and posttreatment were registered with respect to the palatal structures. The movement of the maxillary central incisors and morphologic changes in the anterior alveolar bone were evaluated quantitatively. RESULTS: Displacement in the palatal direction was observed in the alveolar bone around the incisors and the interdental septum. The displacement and bone remodeling/tooth movement ratio were larger on the labial side than the palatal side, and decreased progressively from the crest to apex level. The bone thickness was significantly increased on the labial side and decreased on the palatal side. CONCLUSIONS: Regional differences exist in morphologic changes of the alveolar bone during anterior tooth retraction using TADs. Attention should be paid to the crest region of the palatal alveolar bone because of its small original thickness and low remodeling activity.

Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis.

In vertebrates, new bone formation via intramembranous osteogenesis is a critical biological event for development, remodeling, and fracture healing of bones. Chemotaxis of osteoblast lineage cells is an essential cellular process in new bone formation. Connective tissue growth factor (CTGF) is known to exert chemotactic properties on various cells; however, details of CTGF function in the chemotaxis of osteoblast lineage cells and underlying molecular biological mechanisms have not been clarified. The aim of the present study was to evaluate the chemotactic properties of CTGF and its underlying mechanisms during active bone formation through intramembranous osteogenesis. In our mouse tensile force-induced bone formation model, preosteoblasts were aggregated at the osteogenic front of calvarial bones. CTGF was expressed at the osteogenic front, and functional inhibition of CTGF using a neutralizing antibody suppressed the aggregation of preosteoblasts. In vitro experiments using µ-slide chemotaxis chambers showed that a gradient of CTGF induced chemotaxis of preosteoblastic MC3T3-E1 cells, while a neutralizing integrin α5 antibody and a Ras inhibitor inhibited the CTGF-induced chemotaxis of MC3T3-E1 cells. These findings suggest that the CTGF-integrin α5-Ras axis is an essential molecular mechanism to promote chemotaxis of preosteoblasts during new bone formation through intramembranous osteogenesis.

Scleraxis upregulated by transforming growth factor-ß1 signaling inhibits tension-induced osteoblast differentiation of priodontal ligament cells via ephrin A2.

During tooth movement in orthodontic treatment, bone formation and resorption occur on the tension and compression sides of the alveolar bone, respectively. Although the bone formation activity increases in the periodontal ligament (PDL) on the tension side, the PDL itself is not ossified and maintains its homeostasis, indicating that there are negative regulators of bone formation in the PDL. Our previous report suggested that scleraxis (Scx) has an inhibitory effect on ossification of the PDL on the tension side through the suppression of calcified extracellular matrix formation. However, the molecular biological mechanisms of Scx-modulated inhibition of ossification in the tensioned PDL are not fully understood. The aim of the present study is to clarify the inhibitory role of Scx in osteoblast differentiation of PDL cells and its underlying mechanism. Our in vivo experiment using a mouse experimental tooth movement model showed that Scx expression was increased during early response of the PDL to tensile force. Scx knockdown upregulated expression of alkaline phosphatase, an early osteoblast differentiation marker, in the tensile force-loaded PDL cells in vitro. Transforming growth factor (TGF)-ß1-Smad3 signaling in the PDL was activated by tensile force and inhibitors of TGF-ß receptor and Smad3 suppressed the tensile force-induced Scx expression in PDL cells. Tensile force induced ephrin A2 (Efna2) expression in the PDL and Efna2 knockdown upregulated alkaline phosphatase expression in PDL cells under tensile force loading. Scx knockdown eliminated the tensile force-induced Efna2 expression in PDL cells. These findings suggest that the TGF-ß1-Scx-Efna2 axis is a novel molecular mechanism that negatively regulates the tensile force-induced osteoblast differentiation of PDL cells.

Methionine Enkephalin Suppresses Osteocyte Apoptosis Induced by Compressive Force through Regulation of Nuclear Translocation of NFATc1.

Mechanical stress stimulates bone remodeling, which occurs through bone formation and resorption, resulting in bone adaptation in response to the mechanical stress. Osteocytes perceive mechanical stress loaded to bones and promote bone remodeling through various cellular processes. Osteocyte apoptosis is considered a cellular process to induce bone resorption during mechanical stress-induced bone remodeling, but the underlying molecular mechanisms are not fully understood. Recent studies have demonstrated that neuropeptides play crucial roles in bone metabolism. The neuropeptide, methionine enkephalin (MENK) regulates apoptosis positively and negatively depending on cell type, but the role of MENK in osteocyte apoptosis, followed by bone resorption, in response to mechanical stress is still unknown. Here, we examined the roles and mechanisms of MENK in osteocyte apoptosis induced by compressive force. We loaded compressive force to mouse parietal bones, resulting in a reduction of MENK expression in osteocytes. A neutralizing connective tissue growth factor (CTGF) antibody inhibited the compressive force-induced reduction of MENK. An increase in osteocyte apoptosis in the compressive force-loaded parietal bones was inhibited by MENK administration. Nuclear translocation of NFATc1 in osteocytes in the parietal bones was enhanced by compressive force. INCA-6, which inhibits NFAT translocation into nuclei, suppressed the increase in osteocyte apoptosis in the compressive force-loaded parietal bones. NFATc1-overexpressing MLO-Y4 cells showed increased expression of apoptosis-related genes. MENK administration reduced the nuclear translocation of NFATc1 in osteocytes in the compressive force-loaded parietal bones. Moreover, MENK suppressed Ca2+ influx and calcineurin and calmodulin expression, which are known to induce the nuclear translocation of NFAT in MLO-Y4 cells. In summary, this study shows that osteocytes expressed MENK, whereas the MENK expression was suppressed by compressive force via CTGF signaling. MENK downregulated nuclear translocation of NFATc1 probably by suppressing Ca2+ signaling in osteocytes and consequently inhibiting compressive force-induced osteocyte apoptosis, followed by bone resorption. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Body Weight Reduction of 5% Improved Blood Pressure and Lipid Profiles in Obese Men and Blood Glucose in Obese Women: A Four-Year Follow-up Observational Study.

Background: Body weight reduction (BWR) of at least 3% in obese Japanese individuals through lifestyle interventions has improved the risk factors for cardiovascular disease (CVD). We aimed to assess the relation between body weight change (BWC) and CVD risk change and to identify lifestyle improvement related to BWR in obese Japanese individuals. Methods: Subjects were 2579 health checkup examinees without medicated diabetes, hypertension or dyslipidemia, and a body mass index ≥25 kg/m2 who completed lifestyle questionnaires in 2008 and 2012. The 4-year changes in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, and blood pressure (BP) levels were compared across the five groups based on the 4-year BWC, and presented as <-5%, -5% to -3%, -3% to -1%, -1% to 1%, and ≥1%. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for lifestyle improvement related to BWR. Results: Comparing the groups to the reference group (BWC ranging from -1% to +1%), we observed that FPG and HbA1c levels were lower in women in the <-5% group; BP levels were also lower in the <-5% group; triglyceride levels had improved in the <-3% group, and low-density lipoprotein cholesterol levels in the <-5% group; high-density lipoprotein cholesterol levels had improved in men in the <-5% group. In men, the adjusted OR (95% CI) for BWR related to lifestyle improvement pertaining to "over 30 min exercise" was 2.6 (2.0-3.6). In women, the adjusted ORs for BWR related to "walking or physical activity," "drinking alcohol," and "drinking more than a glass of sake" were 1.7 (1.1-2.7), 1.9 (1.1-3.5), and 1.8 (1.1-3.0), respectively. Conclusions: A 5% BWR improved FPG and HbA1c levels in obese women, and BP and lipid levels in obese men. Improvements in exercise and alcohol consumption habits were associated with BWR in this population.

Serum lipid management in patients with type 1 and type 2 diabetes: a hospital-based cohort study.

INTRODUCTION: Serum lipid management is important for patients with diabetes; however, it has not been examined in our specialized diabetes clinic. AIMS: The aim of the study was to assess the percentage of patients who did not achieve management targets (MT) for low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG), and explore factors related to failure to achieve lipid MT in Japanese patients with type 1 (T1D) and type 2 diabetes (T2D). METHODS: This cross-sectional study included 795 patients (35% men) with T1D and 4018 patients (60% men) with T2D attending our diabetes center. MTs for serum lipids were in accordance with the guidelines of the Japan Atherosclerosis Society. Logistic regression analysis was performed to identify factors related to failure to achieve MTs for serum lipids. RESULTS: The percentages of men/women who did not achieve MT for LDL-C were 34.1/31.8% in T1D and 40.5/52.7% in T2D. The corresponding values for TG were 35.1/14.0% in T1D and 50.1/47.9% in T2D, and for HDL-C were 2.5/0% in T1D and 8.6/2.9% in T2D. Increase in body mass index (BMI) and glycated hemoglobin (HbA1c) were significantly and independently associated with failure to achieve lipid MT in patients with T1D and T2D for both sexes. CONCLUSIONS: The percentages of our patients who did not achieve serum lipid MT were relatively high in T1D and T2D, and higher HbA1c and BMI were associated with failure to achieve serum lipid MTs. More attention should be paid to lipid management in patients with diabetes especially who have higher HbA1c and BMI in our facility.

Diabetes diagnostic thresholds of the glycated hemoglobin A1c and fasting plasma glucose levels considering the 5-year incidence of retinopathy.

AIMS: As retinopathy is used as a defining threshold of diabetes, we assessed the glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) values associated with an increased risk of 5-year incidence of retinopathy. METHODS: We studied HbA1c, FPG, and optic fundus findings of 2605 individuals without previously diagnosed diabetes annually during a 5-year period. Retinopathy was examined using non-mydriatic, 45° digital fundus photography. Baseline levels were stratified as <5.3 [34], 5.3-5.6 [34-38], 5.7-6.0 [39-42], 6.1-6.4 [43-47], and ⩾6.5% [48mmol/mol] for HbA1c and <5.0, 5.0-5.5, 5.6-6.0, 6.1-6.9, and ⩾7.0mmol/L for FPG. Cox proportional hazard models were used to analyze hazard ratios (HRs) associated with HbA1c or FPG for incident retinopathy. RESULTS: During a total of 11845 person-years, we identified 50 (1.9%) cases of incident retinopathy. The adjusted HRs for incident retinopathy associated with a one-standard deviation increase in HbA1c and FPG were 1.2 (95% confidence intervals: 1.1-1.4) and 1.2 (1.1-1.4), respectively. These HRs were significantly higher for a HbA1c level ⩾6.5% (48mmol/mol) (3.4 [1.1-10.2]) or FPG level ⩾7.0mmol/L (3.6 [1.1-11.6]) than for a HbA1c level <5.3% (34mmol/mol) or FPG level <5.0mmol/L. CONCLUSIONS: A HbA1c value of 6.5% (48mmol/mol) and FPG value of 7.0mmol/L might be proper as diabetes diagnostic thresholds that indicate a high risk of future retinopathy.

Associations of HbA1c and fasting plasma glucose with incident diabetes: Implications for pre-diabetes thresholds in a Japanese population.

AIMS: This study assessed pre-diabetes (pre-DM) cutoffs for HbA1c and fasting plasma glucose (FPG) that were associated with an increased risk of incident DM. METHODS: We evaluated 2267 non-diabetic Japanese health-check examinees (HbA1c: <6.5% [<48mmol/mol] and FPG: <7.0mmol/L) who were 30-79 years old and were followed-up for 5 years. Incident DM was defined as HbA1c of ≥6.5% (≥48mmol/mol), FPG of ≥7.0mmol/L, or physician-diagnosed DM. RESULTS: During 11047 person-years, we identified 99 incident DM cases (4.3%). The incidence of DM increased with increasing baseline HbA1c or FPG levels, and the change points (95% confidence intervals) were 5.7% (5.6-5.7%; 39mmol/mol [38-39mmol/mol]) for HbA1c and 5.5mmol/L (5.5-5.6mmol/L) for FPG. The adjusted hazard ratios (HRs) for incident DM per one standard deviation-increase in HbA1c and FPG were 5.5 (4.4-6.8) and 4.0 (3.2-4.8), respectively. The adjusted HRs for incident DM were significantly higher at HbA1c of 5.7-6.4% (39-46mmol/mol) or FPG of 5.5-6.9mmol/L, compared to HbA1c of <5.7% (<39mmol/mol) or FPG of <5.5mmol/L. CONCLUSION: The lower cut-offs for pre-DM may be 5.7% (39mmol/mol) for HbA1c and 5.5mmol/L for FPG in this Japanese population.

Acupuncture-induced changes of vagal function in patients with depression: A preliminary sham-controlled study with press needles.

To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72 h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Beck's Depression Inventory scores (P = 0.031), systolic/diastolic blood pressures (P = 0.002/P = 0.011), and coefficient of variation of the R-R interval (P < 0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Beck's Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression.