The significant role of glycosaminoglycans in tooth development.

This review delves into the roles of glycosaminoglycans (GAGs), integral components of proteoglycans, in tooth development. Proteoglycans consist of a core protein linked to GAG chains, comprised of repeating disaccharide units. GAGs are classified into several types, such as hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, and keratan sulfate. Functioning as critical macromolecular components within the dental basement membrane, these GAGs facilitate cell adhesion and aggregation, and play key roles in regulating cell proliferation and differentiation, thereby significantly influencing tooth morphogenesis. Notably, our recent research has identified the hyaluronan-degrading enzyme Transmembrane protein 2 (Tmem2) and we have conducted functional analyses using mouse models. These studies have unveiled the essential role of Tmem2-mediated hyaluronan degradation and its involvement in hyaluronan-mediated cell adhesion during tooth formation. This review provides a comprehensive summary of the current understanding of GAG functions in tooth development, integrating insights from recent research, and discusses future directions in this field.

Reciprocal first night effect on rhythmic and non-rhythmic oromotor episodes in moderate to severe primary sleep bruxism: A retrospective physiological study.

BACKGROUND: Sleep on the first night in a sleep laboratory is characterized by a lower sleep quality and frequency of rhythmic masticatory muscle activity (RMMA) than that on the second night in moderate to severe sleep bruxism (SB) patients. OBJECTIVE: The aims of this study was to clarify the physiological factors contributing to the first night effect on oromotor activity during sleep and investigate whether physiological factors involved in the first night effect differed between rhythmic and non-rhythmic oromotor activities. METHODS: Polysomnographic data collected on two consecutive nights from 15 moderate to severe SB subjects (F 7: M 8; age: 23.2 ± 1.3 [mean ± SD] years) were retrospectively analysed. Sleep variables, RMMA and non-specific masticatory muscle activity (NSMA) were scored in relation to episode types (i.e. phasic or tonic and cluster or isolated), sleep architecture and transient arousals. The relationships between nightly differences in oromotor and sleep variables were assessed. The distribution of oromotor events, arousals, cortical electroencephalographic power, RR intervals and heart rate variability were examined in relation to sleep cycle changes. These variables were compared between the first and second nights and between RMMA and NSMA. RESULTS: Sleep variables showed a lower sleep quality on Night 1 than on Night 2. In comparisons with Night 1, the RMMA index increased by 18.8% (p < .001, the Wilcoxon signed-rank test) on Night 2, while the NSMA index decreased by 17.9% (p = .041). Changes in the RMMA index did not correlate with those in sleep variables, while changes in the NSMA index correlated with those in arousal-related variables (p < .001, Spearman's rank correlation). An increase in the RMMA index on Night 2 was found for the cluster type and stage N1 related to sleep cyclic fluctuations in cortical and cardiac activities. In contrast, the decrease in the NSMA index was associated with increases in the isolated type and the occurrence of stage N2 and wakefulness regardless of the sleep cycle. CONCLUSION: Discrepancies in first night effect on the occurrence of RMMA and NSMA represent unique sleep-related processes in the genesis of oromotor phenotypes in SB subjects.

Sleep architecture as a candidate for phenotyping sleep bruxism: A narrative physiological review.

BACKGROUND: Sleep bruxism (SB), an oral behaviour in otherwise healthy individuals, is characterised by frequent rhythmic masticatory muscle activity (RMMA) during sleep. RMMA/SB episodes occur over various sleep stages (N1-N3 and rapid eye movement (REM)), sleep cycles (non-REM to REM), and frequently with microarousals. It currently remains unclear whether these characteristics of sleep architecture are phenotype candidates for the genesis of RMMA/SB. OBJECTIVES: This narrative review investigated the relationship between sleep architecture and the occurrence of RMMA as a SB phenotype candidate. METHODS: PubMed research was performed using keywords related to RMMA/SB and sleep architecture. RESULTS: In non-SB and SB healthy individuals, RMMA episodes were most frequent in the light non-REM sleep stages N1 and N2, particularly during the ascending phase of sleep cycles. The onset of RMMA/SB episodes in healthy individuals was preceded by a physiological arousal sequence of autonomic cardiovascular to cortical activation. It was not possible to extract a consistent sleep architecture pattern in the presence of sleep comorbidities. The lack of standardisation and variability between subject complexified the search for specific sleep architecture phenotype(s). CONCLUSION: In otherwise healthy individuals, the genesis of RMMA/SB episodes is largely affected by oscillations in the sleep stage and cycle as well as the occurrence of microarousal. Furthermore, a specific sleep architecture pattern cannot be confirmed in the presence of sleep comorbidity. Further studies are needed to delineate sleep architecture phenotype candidate(s) that contribute to the more accurate diagnosis of SB and treatment approaches using standardised and innovative methodologies.

Three-dimensional changes in the cranial base associated with soft-diet feeding.

BACKGROUND: Masticatory activity affects the morphology of the maxillo-mandibular complex, however, its influence on the cranial base remains to be elucidated. The recent integration of quantitative morphometric analysis with 3D imaging enabled a comprehensive and high-resolution morphological characterization of the craniofacial complex. We aimed to investigate the influence of masticatory activity on the morphology of the growing cranial base by three-dimensional (3D) geometric morphometric approach using micro-CT. METHODS: The micro-CT data was reanalyzed to illustrate the 3D shape of the cranial base, and wireframe models were generated by connecting landmarks on the images. In the original study, mice were fed a soft diet (SD) of powdered pellets or a conventional hard diet (HD) for 6 weeks from 3 to 9 weeks of age, immediately after weaning. A principal component (PC) analysis analyzed shape variations and assessed their significance, while canonical variate (CV) analysis facilitated the comparison and differentiation of groups based on shape, unveiling meaningful shape distinctions. RESULTS: Three PCs were extracted that significantly separated the SD and HD groups among those explaining variations in shape. These PCs were related to the length of the sphenoid bone, the width of the anterior part of the sphenoid bone, and the length of the cranial base. Furthermore, one CV effectively distinguished SD from HD, and CV analysis showed that the sphenoid was shortened in the length and narrowed at the border of the temporal bone in SD mice. CONCLUSIONS: Masticatory loading affects the skeletal development of the cranial base. The morphology of the sphenoid bone was affected in both the sagittal and transverse axes.

The influence of age on the frequency of rhythmic masticatory muscle activity during sleep in general population differs from that in clinical research samples.

BACKGROUND: During sleep, limb and jaw muscle motor activity can be quantified by electromyography (EMG). The frequency of periodic limb activity during sleep increases with age in both the general and clinical research populations. The literature is controversial regarding stability, over age, of the frequency of rhythmic masticatory muscle activity (RMMA), which is one biomarker of sleep bruxism (SB). OBJECTIVES: The purpose of this retrospective sleep laboratory study was to assess if any change in RMMA frequency occurs over age in the general population (GP) and two clinical research (CR) samples. METHODS: RMMA signals from polysomnography (PSG) recordings of 465 individuals, irrespective of SB awareness, were analysed. The sample comprised 164 individuals from the GP of Sao Paulo, and 301 individuals from Montreal and Osaka CR samples. Data were divided into two subgroups, younger (15-39) and older (40-80) participants. RMMA was classified as low frequency (<2 events/h) or high (≥2 events/h). Pearson correlation (R) and B (slope) analyses were performed with power estimations. RESULTS: In the GP sample, no significant change over age was noted in the RMMA index/year. In the CR samples, a significant reduction was observed in the RMMA index/year (-0.05) with age (R2  = .042; p < .001; 3.5 to 1.5 RMMA/h from 20 to 60 years old). CONCLUSIONS: In the GP, the RMMA index remained stable over age. In the CR samples, a significant, reduction was observed. Prospective studies with multiple home sleep recordings, in both general and clinical research populations, are needed before extrapolating from the present findings.

Prevalence of saliva immunoglobulin A antibodies reactive with severe acute respiratory syndrome coronavirus 2 among Japanese people unexposed to the virus.

While the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to public health as the number of cases and COVID-19-related deaths are increasing worldwide, the incidence of the virus infection is extremely low in Japan compared with many other countries. To explain this uncommon phenomenon, we investigated the prevalence of naturally occurring ("natural") antibodies, focusing on those of the secretory immunoglobulin A (sIgA) form, reactive with SARS-CoV-2 among Japanese people. One hundred and eighty healthy Japanese volunteers of a wide range of age who had been considered to be unexposed to SARS-CoV-2 participated in this study. Saliva samples and blood samples were collected from all of the 180 participants and 139 adults (aged ≥ 20 years) included therein, respectively. The determination of saliva IgA antibodies, mostly comprising sIgA antibodies, as well as serum IgA and immunoglobulin G antibodies, reactive with the receptor binding domain of the SARS-CoV-2 spike-1 subunit proteins was conducted using an enzyme-linked immunosorbent assay. The major findings were that 52.78% (95% confidence interval, 45.21%-60.25%) of the individuals who had not been exposed to SARS-CoV-2 were positive for saliva IgA antibodies with a wide range of levels between 0.002 and 3.272 ng/mL, and that there may be a negative trend in positivity for the antibodies according to age. As we had expected, a frequent occurrence of assumable "natural" sIgA antibodies reactive with SARS-CoV-2 among the studied Japanese participant population was observed.

Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis.

Cleft palate is one of the major congenital craniofacial birth defects. The etiology underlying the pathogenesis of cleft palate has yet to be fully elucidated. Dissociation of the medial edge epithelium (MEE) at the contacting region of palatal shelves and subsequent migration or apoptosis of MEE cells is required for proper MEE removal. Ras-responsive element-binding protein 1 (RREB1), a RAS transcriptional effector, has recently been shown to play a crucial role in developmental epithelial-mesenchymal transition (EMT), in which loss of epithelial characteristics is an initial step, during mid-gastrulation of embryonic development. Interestingly, the involvement of RREB1 in cleft palate has been indicated in humans. Here, we demonstrated that pan-Ras inhibitor prevents the dissociation of MEE during murine palatal fusion. Rreb1 is expressed in the palatal epithelium during palatal fusion, and knockdown of Rreb1 in palatal organ culture resulted in palatal fusion defects by inhibiting the dissociation of MEE cells. Our present findings provide evidence that RREB1-mediated Ras signaling is required during palatal fusion. Aberrant RREB1-mediated Ras signaling might be involved in the pathogenesis of cleft palate.

Relationships between cortical, cardiac, and arousal-motor activities in the genesis of rhythmic masticatory muscle activity across sleep cycles in primary sleep bruxism children.

STUDY OBJECTIVES: The present study aimed to clarify the physiological relationships between rhythmic masticatory muscle activity (RMMA) and cyclic changes in cortical, autonomic, and arousal-motor activities during sleep in sleep bruxism (SB) children. METHODS: Polysomnographic recordings were performed on 15 SB children (9 boys, 6 girls, 10.3 ± 2.5 years) and 18 control children (5 boys, 13 girls, 10.7 ± 3.1 years) free from sleep and developmental disorders. Sleep and RMMA were scored by the standard rules. Sleep cycle was divided into NREM and REM sleep segments and the frequency of RMMA, transient arousal and movement, and cortical and cardiac activities were then quantitatively analyzed in relation to sleep cycles. RESULTS: Neither sleep architecture nor sleep stage distribution of RMMA significantly differed between the two groups. In sleep cycles, SB children showed more frequent RMMA in all segments than controls, while cyclic changes in cortical and autonomic activities did not significantly differ between the two groups. In SB children, RMMA was the most frequent in the last NREM segment before REM sleep and was associated with increases in cortical beta activity and arousal; more than 70% of RMMA time-dependently occurred with cortical and motor arousals. CONCLUSIONS: This is the first study to suggest that the potentiation of RMMA occurrence was associated with transient arousal under cyclic sleep processes in primary SB children.

First night effect on polysomnographic sleep bruxism diagnosis varies among young subjects with different degrees of rhythmic masticatory muscle activity.

OBJECTIVE: This study investigated the first night effect on the polysomnographic diagnosis of sleep bruxism (SB). METHODS: Polysomnographic recordings were performed for two consecutive nights in forty-three subjects (mean age 23.7 ± 0.32 years [range: 20.0-33.0]). Sleep variables and rhythmic masticatory muscle activity (RMMA) were scored for two nights. The diagnosis of SB was graded by the frequency of RMMA with cut-off values of two and four times per hour of sleep. RESULTS: Participants were classified into control (n = 15), low (n = 13) and moderate-high (n = 15) groups. Among the three groups, the concordance of the SB diagnosis was compared between the two nights. Sleep variables showed a significant first-night effect with lower sleep efficiency, longer sleep latency and higher frequency of arousals. The frequency of RMMA significantly increased from the first to the second night in the moderate-high SB group only. The concordance rate of the severity between the two nights was 93.3% (14/15) in the control group, 76.9% (10/13) in the low SB group and 60% (9/15) in the moderate-high SB group. When the severity was determined on the first night, it remained the same on the second night in 77.8% (14/18) of the control group, 66.7% (10/15) of the low SB group and 90.0% (9/10) of the moderate-high SB group. CONCLUSION: The results showed that the first night effect on the occurrence of RMMA differed among the different degrees of the RMMA frequency, and suggest that, due to the first night effect, single-night polysomnography may underestimate the moderate-high level of SB but differentiate the low level of SB from controls.

Sleep stage dynamics in young patients with sleep bruxism.

STUDY OBJECTIVES: We hypothesized that sleep stage dynamics are different in patients with sleep bruxism (SB) and that these changes are associated with the occurrence of rhythmic masticatory muscle activity (RMMA). METHODS: Fifteen healthy controls and 15 patients with SB underwent overnight polysomnography. Sleep variables and survival curves of continuous runs of each sleep stage were compared between the groups. Stage transition dynamics and the probability of stage fragmentation were analyzed for three epochs before and after the epoch with RMMA. Survival curves of continuous runs of each sleep stage, terminated with or without RMMA, were also compared. RESULTS: There were no significant differences in sleep variables between the groups, except for shorter sleep latency, shorter rapid eye movement (REM) latency, and longer total N1 duration in SB patients than in controls. REM sleep and N2 were significantly less continuous in SB patients than in controls. In the SB group, stage fragmentation probability was significantly increased for the epoch with RMMA compared with the baseline for all stages. Meanwhile, the occurrence of RMMA did not affect the continuity of N2 or REM; however, the occurrence of RMMA was preceded by more continuous N3 runs. CONCLUSIONS: Sleep stage dynamics differed between SB patients and controls. RMMA does not result in sleep disruption but is likely associated with dissipation of sleep pressure. Less continuity of REM sleep in SB may provide insights into the underlying pathophysiological mechanisms of SB, which may be related to REM sleep processes such as cortical desynchronized states or brainstem activation.