GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence

Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively

Malocclusion impairs cognitive behavior via AgRP signaling in adolescent mice

IntroductionOcclusal disharmony induced by deteriorating oral health conditions, such as tooth loss and decreased masticatory muscle due to sarcopenia, is one of the causes of cognitive impairment. Chewing is an essential oral function for maintaining cognitive function not only in the elderly but also in young people. Malocclusion is an occlusal disharmony that commonly occurs in children. The connection between a decline in cognitive function and malocclusion in children has been shown with chronic mouth breathing, obstructive sleep apnea syndrome, and thumb/digit sucking habits. However, the mechanism of malocclusion-induced cognitive decline is not fully understood. We recently reported an association between feeding-related neuropeptides and cognitive decline in adolescent mice with activity-based anorexia. The aim of the present study was to assess the effects of malocclusion on cognitive behavior and clarify the connection between cognitive decline and hypothalamic feeding-related neuropeptides in adolescent mice with malocclusion.MethodsFour-week-old mice were randomly assigned to the sham-operated solid diet-fed (Sham/solid), sham-operated powder diet-fed (Sham/powder), or malocclusion-operated powder diet-fed (Malocclusion/powder) group. We applied composite resin to the mandibular anterior teeth to simulate malocclusion. We evaluated cognitive behavior using a novel object recognition (NOR) test, measured hypothalamic feeding-related neuropeptide mRNA expression levels, and enumerated c-Fos-positive cells in the hypothalamus 1 month after surgery. We also evaluated the effects of central antibody administration on cognitive behavior impairment in the NOR test.ResultsThe NOR indices were lower and the agouti-related peptide (AgRP) mRNA levels and number of c-Fos-positive cells were higher in the malocclusion/powder group than in the other groups. The c-Fos-positive cells were also AgRP-positive. We observed that the central administration of anti-AgRP antibody significantly increased the NOR indices.DiscussionThe present study suggests that elevated cerebral AgRP signaling contributes to malocclusion-induced cognitive decline in adolescents, and the suppression of AgRP signaling can be a new therapeutic target against cognitive decline in occlusal disharmony

Micrognathia with temporomandibular joint ankylosis and obstructive sleep apnea treated with mandibular distraction osteogenesis using skeletal anchorage: a case report

Abstract Background We describe the case of a 16-year-old female patient with micrognathia, temporomandibular joint (TMJ) ankylosis, and obstructive sleep apnea, who was treated with mandibular distraction osteogenesis (DO) combined with sliding genioplasty, using skeletal anchorage. Case presentation We first performed interpositional arthroplasty, in which an interposition of fascia temporalis and surrounding fat tissue was inserted into the defect after bilateral condylectomy, increasing the maximum mouth opening from 5.0 to 32.0 mm. Subsequently, orthodontic treatment and advancement of the mandible were carried out by mandibular DO, using miniscrews and miniplates. Finally, sliding genioplasty was performed to bring the tip of the mandible forward. The total amount of mandibular advancement at the menton was 16.0 mm. An improved facial appearance and good occlusion were eventually achieved, and the apnea-hypopnea index decreased from 37.1 to 8.7. There was no obvious bone resorption or pain in the temporomandibular region, limited mouth opening (maximum mouth opening: 33.0 mm), myofascial pain or headache, downward rotation of the mandible, or lateral shift of mandibular position evident at 5 years and 6 months after mandibular DO. Conclusion Mandibular DO using skeletal anchorage with intermaxillary elastics is useful for preventing extrusion of the upper and lower anterior teeth, thereby preventing rotation of the mandible. In addition, mandibular DO combined with sliding genioplasty is effective at improving both dentofacial deformities and impaired respiratory function

A relation between osteoclastogenesis inhibition and membrane-type estrogen receptor GPR30

AbstractDisruption of the cooperative balance between osteoblasts and osteoclasts causes various bone disorders, some of which are because of abnormal osteoclast recruitment. Osteoporosis, one of the bone disorders, is not effectively treated by currently available medicines. In addition to the development of novel drugs for palliative treatment, the exploitation of novel compounds for preventive treatment is important in an aging society. Quercetin, a major flavonoid found in many fruits and vegetables, has been expected to inhibit cancer and prevent several diseases because of its anti-inflammatory and estrogenic functions. It has been reported that quercetin has the potential to reduce bone resorption, but the mechanism by which this compound affects the differentiation of osteoclasts remains unknown. Here, using a bone marrow cell-based in vitro osteoclast differentiation system from bone marrow cells, we found that the ability of quercetin to inhibit osteoclastogenesis was related to its estrogenic activity. The inhibition was partially blocked by a specific antagonist for the nuclear receptor estrogen receptor α, but a specific antagonist of the membrane-type receptor GPR30 completely ablated this inhibition. Furthermore, quercetin suppressed the transient increase of Akt phosphorylation induced by the stimulation of macrophage colony-stimulating factor and receptor activator of NF-κB ligand with no effect on MAPK phosphorylation, suggesting exquisite crosstalk between cytokine receptor and G-protein coupled receptor signaling. These results indicate the important role of GPR30 in osteoclast differentiation and provide new insights to the development of new treatments for osteoporosis