Relationship between risk of oral frailty and awareness of oral frailty among community-dwelling adults: a cross-sectional study.

We aimed to investigate the relationship between the risk of oral frailty and awareness of oral frailty among Japanese adults in an adult dental health field study conducted in Kanagawa Prefecture. Questionnaire data from a total of 5051 individuals (1907 males, 3144 females; mean age; 59.9 years) were used. The risk of oral frailty was assessed using the Oral Frailty Index-8. Of the participants, 1418 (28.1%) had a high risk of oral frailty and 1495 (29.6%) had knowledge of oral frailty. Logistic regression analysis indicated that the risk of oral frailty was significantly associated with awareness of oral frailty. We further found that awareness of oral frailty was significantly related to gender (female), age (20-39 compared to 70-79, ≥ 80), residential areas (Yokohama compared to Kawasaki, Sagamihara), exercise habits (yes), eating a balanced diet (yes), consciousness of oral health (yes), risk of oral frailty (low) and outpatient category (hospital visit). For groups with low levels of awareness obtained from the results of this study, it is necessary to consider the means of accessibility and increase awareness further.

Exploring the Role of IL-17A in Oral Dysbiosis-Associated Periodontitis and Its Correlation with Systemic Inflammatory Disease.

Oral microbiota play a pivotal role in maintaining homeostasis, safeguarding the oral cavity, and preventing the onset of disease. Oral dysbiosis has the potential to trigger pro-inflammatory effects and immune dysregulation, which can have a negative impact on systemic health. It is regarded as a key etiological factor for periodontitis. The emergence and persistence of oral dysbiosis have been demonstrated to mediate inflammatory pathology locally and at distant sites. The heightened inflammation observed in oral dysbiosis is dependent upon the secretion of interleukin-17A (IL-17A) by various innate and adaptive immune cells. IL-17A has been found to play a significant role in host defense mechanisms by inducing antibacterial peptides, recruiting neutrophils, and promoting local inflammation via cytokines and chemokines. This review seeks to present the current knowledge on oral dysbiosis and its prevention, as well as the underlying role of IL-17A in periodontitis induced by oral dysbiosis and its impact on systemic inflammatory disease.

Association between Periodontal Condition and Fat Distribution in Japanese Adults: A Cross-Sectional Study Using Check-Up Data.

Some studies have reported a significant association between periodontal condition and obesity status. We hypothesized that visceral fat area (VFA) and subcutaneous fat area (SFA) volumes might be correlated with periodontal condition. The purpose of the present cross-sectional study was to investigate the association between periodontal condition and fat distribution in Japanese adults. A total of 158 participants, aged 35-74 years, underwent a health check-up including fat distribution and oral examinations. All of the participants underwent magnetic resonance imaging to quantify VFA and SFA. Periodontal condition was evaluated using the periodontal pocket depth (PPD) and clinical attachment level. The VFA volumes differed among the PPD score and clinical attachment level (CAL) code groups. On the other hand, no significant differences in SFA volume were observed among different periodontal conditions. Multiple regression analysis showed that VFA was positively correlated with a greater CAL (standardized coefficient ß = 0.123, p = 0.009), but not with a greater PPD score. A larger VFA was positively associated with a greater CAL in Japanese adults, whereas no association was found between SFA and periodontal condition.

Occupational Difference in Oral Health Status and Behaviors in Japanese Workers: A Literature Review.

The occupational environment is an important factor for oral health because people spend a long time in the workplace throughout their lives and are affected by work-related stress and occupational health policies. This study aimed to review evidence for the association between occupation and oral health status and behaviors. A literature search of PubMed was conducted from February to May 2022, as well as a manual search analyzing the article origins. Articles were screened and considered eligible if they met the following criteria: (1) published in English; (2) epidemiological studies on humans; and (3) examined the association between occupation and oral health status and behaviors. All 23 articles identified met the eligibility criteria. After full-text assessments, ten articles from Japan were included in this review: four on the association between occupation and dental caries, three on occupation and periodontal disease, two on occupation and tooth loss, and one on occupation and oral health behaviors. An association was apparent between occupation, oral health status and behaviors among Japanese workers. In particular, skilled workers, salespersons, and drivers who work longer hours and often on nightshifts, tended to have poor oral health.

Evolution of the Human Brain Can Help Determine Pathophysiology of Neurodevelopmental Disorders.

The evolution of humans brought about a co-occurring evolution of the human brain, which is far larger and more complex than that of many other organisms. The brain has evolved characteristically in humans in many respects, including macro-and micro-anatomical changes in the brain structure, changes in gene expression, and cell populations and ratios. These characteristics are essential for the execution of higher functions, such as sociality, language, and cognition, which express humanity, and are thought to have been acquired over evolutionary time. However, with the acquisition of higher functions also comes the risk of the disease in which they fail. This review focuses on human brain evolution and neurodevelopmental disorders (NDDs) and discusses brain development, molecular evolution, and human brain evolution. Discussing the potential for the development and pathophysiology of NDDs acquired by human brain evolution will provide insights into the acquisition and breakdown of higher functions from a new perspective.

MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.

Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage.

During brain development, neural stem cells (NSCs) initially produce neurons and change their fate to generate glias. While the regulation of neurogenesis is well characterized, specific markers for glial precursor cells (GPCs) and the master regulators for gliogenesis remain unidentified. Accumulating evidence suggests that RNA-binding proteins (RBPs) have significant roles in neuronal development and function, as they comprehensively regulate the expression of target genes in a cell-type-specific manner. We systematically investigated the expression profiles of 1,436 murine RBPs in the developing mouse brain and identified quaking (Qk) as a marker of the putative GPC population. Functional analysis of the NSC-specific Qk-null mutant mouse revealed the key role of Qk in astrocyte and oligodendrocyte generation and differentiation from NSCs. Mechanistically, Qk upregulates gliogenic genes via quaking response elements in their 3' untranslated regions. These results provide crucial directions for identifying GPCs and deciphering the regulatory mechanisms of gliogenesis from NSCs.

Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults.

Deep and subcortical white matter hyperintensity (DSWMH) lesions are a small-vessel disease of the brain. The aim of this cross-sectional study was to investigate the relationship between DSWMH lesions and periodontal status in Japanese adults who participated in a health check. We enrolled 444 consecutive participants (mean age, 54.5 years) who received both brain and oral health evaluation services at the Asahi University Hospital. Magnetic resonance imaging was used to detect DSWMH lesions. Periodontal status was assessed using the community periodontal index. Of the study participants, 215 (48.4%) had DSWMH lesions. Multivariate logistic regression showed that the presence of DSWMH lesions was significantly related to age ≥ 65 years (vs. < 65 years, odds ratio [OR] = 2.984, 95% confidence interval [CI] = 1.696-5.232), systolic blood pressure ≥ 140 mmHg (vs. < 140 mmHg, OR = 2.579, 95% CI = 1.252-5.314), the presence of ≥ 28 teeth (vs. < 28 teeth, OR = 0.635, 95% CI = 0.420-0.961), and probing pocket depth (PPD) ≥ 6 mm (vs. PPD < 6 mm, OR = 1.948, 95% CI = 1.132-3.354) after adjustment for confounding factors. Having PPD ≥ 6 mm may be a risk factor for DSWMH lesions in Japanese adults.

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis.

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall-associated proteins, including an antigen that stimulates mucosal T helper 17 (TH17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)-dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal TH17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

Awareness of Clenching and Underweight are Risk Factors for Onset of Crowding in Young Adults: A Prospective 3-Year Cohort Study.

Bruxism is a parafunctional activity that can seriously affect quality of life. Although bruxism induces many problems in the oral and maxillofacial area, whether it contributes to the onset of malocclusion remains unclear. The purpose of this prospective cohort study was to investigate the association between the onset of malocclusion and awareness of clenching during the daytime in young adults. Among 1,092 Okayama University students who underwent normal occlusion at baseline, we analysed 238 who had undergone a dental examination and had complete data after 3 years (2013⁻2016). We also performed subgroup analysis to focus on the association between awake bruxism and the onset of crowding (n = 216). Odds ratios (ORs) were calculated using multivariate logistic regression analyses. The incidences of malocclusion and crowding were 53.8% and 44.5%, respectively. In multivariate logistic regression, awareness of clenching was a risk factor for crowding (OR: 3.63; 95% confidence interval [CI]: 1.08⁻12.17). Moreover, underweight (body mass index < 18.5 kg/m²) was related to the onset of malocclusion (OR: 2.34; 95%CI: 1.11⁻4.92) and crowding (OR: 2.52, 95%CI: 1.25⁻5.76). These results suggest that awareness of clenching during the daytime and underweight are risk factors for the onset of crowding in young adults.

Association between Chewing Problems and Sleep among Japanese Adults.

An association between physical illness and sleep has been suggested. Disordered chewing might be a physical factor that is associated with sleep issues. This cross-sectional study aimed to determine whether chewing problems are associated with sleep in Japanese adults. Sleep and chewing issues were evaluated in 6,025 community residents using a self-reported questionnaire. The prevalence of poor sleep quality and sleeping for <6 h/day (short duration) were 15.6% and 29.4%, respectively. Multivariate logistic regression analyses showed that prevalence of poor sleep quality was significantly associated with self-reported medical history (odds ratio (OR), 1.30; p < 0.001), self-reported symptoms (OR, 4.59; p < 0.001), chewing problems (OR, 1.65; p < 0.001), and poor glycemic control (OR, 1.43; p=0.035). The prevalence of short sleep duration was also significantly associated with female sex (OR, 1.23; p=0.001), self-reported symptoms (OR, 1.60; p < 0.001), chewing problems (OR, 1.30; p=0.001), and being overweight (OR, 1.41; p < 0.001). In conclusion, chewing problems were associated with poor sleep quality and short sleep duration among Japanese adults.

Diencephalic progenitors contribute to the posterior septum through rostral migration along the hippocampal axonal pathway.

Septal nuclei are telencephalic structures associated with a variety of brain functions as part of the limbic system. The two posterior septal nuclei, the triangular septal nucleus (TS) and the bed nuclei of the anterior commissure (BAC), are involved in fear and anxiety through their projections to the medial habenular nucleus. However, the development of both the TS and BAC remains unclear. Here, we found a novel caudal origin and putative migratory stream of mouse posterior septal neurons arising from the thalamic eminence (TE), a transient developmental structure at the rostral end of the rodent diencephalon. TE-derived cells, which have glutamatergic identity, migrated rostrally and entered the telencephalic territory by passing beneath the third ventricle. Subsequently, they turned dorsally toward the posterior septum. We also observed that TS and BAC neurons in the postnatal septum were labeled with GFP by in utero electroporation into the TE, suggesting a shared origin. Furthermore, TE-derived septal neurons migrated along the fornix, an efferent pathway from the hippocampus. These results demonstrate that posterior septal neurons have a distinct extratelencephalic origin from other septal nuclei. This heterogeneous origin may contribute to neuronal diversity of the septal nuclear complex.

Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.

Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin, which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II, and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1. In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.

Impact of commensal flora on periodontal immune response to lipopolysaccharide.

BACKGROUND: Commensal flora are involved in the appropriate development of the mature immune system. However, it is unclear how commensal flora contribute to immune responses against periodontal pathogens, including the response to lipopolysaccharide (LPS). The purpose of this study was to evaluate the expression of immune responses after topical application of LPS in germ-free (GF) and specific-pathogen-free (SPF) mice. METHODS: GF and SPF mice at 8 weeks of age were randomly divided into four groups each: a baseline group (n = 4/group) and three experimental groups (n = 6/group). Experimental groups received topical application of Porphyromonas gingivalis LPS (10 µg/µL) into the palatal gingival sulcus. Sampling was performed before LPS application (baseline) and at 3, 24, or 72 hours after LPS application. The numbers of neutrophils, CD4+ , and CD8+ T cells in periodontal tissue were evaluated by immunohistochemistry. Expression of genes encoding cytokines, chemokines, and a transcription factor was determined by real-time PCR. RESULTS: SPF mice, but not GF mice, showed an increased number of CD4+ T cells in the periodontal tissue at 3 hours after LPS application, compared with the number at baseline (p < 0.05). Gene expressions of tumor necrosis factor-α (Tnf-α) and forkhead box protein p3 (Foxp3) was also significantly higher in the SPF mice than in the GF mice at 3 hours after LPS application (p < 0.05). The number of neutrophils peaked at 24 hours in both GF and SPF mice. CONCLUSIONS: LPS-exposed SPF mice exhibited increases in the number of CD4+ T cells and in Tnf-α and Foxp3 gene expression in periodontal tissue compared with LPS-exposed GF mice.

Canonical TGF-ß Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-ß (TGF-ß) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-ß family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-ß family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-ß receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-ß signaling is involved in the pathogenesis of neurodevelopmental diseases.SIGNIFICANCE STATEMENT Canonical transforming growth factor-ß (TGF-ß) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-ß signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-ß signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our results suggest that proper control of TGF-ß/Smads/CRMP2 signaling pathways is critical for the precise execution of neuronal morphogenesis, whose impairment eventually results in neurodevelopmental disorders.

Age-related changes of CD4+ T cell migration and cytokine expression in germ-free and SPF mice periodontium.

OBJECTIVE: Increasing age is a potential risk factor for periodontal tissue breakdown, which may be affected by commensal flora. The aim of this study evaluated age-related changes in CD4+ T cells, C-C chemokine ligand 5 (CCL5), interleukin (IL)-17A, and receptor activator of nuclear factor-kappa B ligand (RANKL) expression using germ-free (GF) and conventionally reared (SPF) mice. DESIGN: GF and SPF mice at 8 (n = 6/group) and 22 weeks old (n = 6/group) were used. Immunohistochemical analyses were performed to determine the effects of aging on protein expression in periodontal tissues. Age-related changes in alveolar bone were quantified using micro-CT analysis. RESULTS: SPF mice, but not GF mice, showed an age-related increase in alveolar bone loss (P < 0.01). SPF mice at 22 weeks of age increased expression of CD4+ T cells, CCL5, IL-17A, and RANKL compared to those at 8 weeks of age in connective tissue and alveolar bone surface (P < 0.01). Furthermore, there was increased CD4+ T cells, which were co-expressed with IL-17A and RANKL in SPF mice at 22 weeks of age. On the other hand, the GF mice did not show any significant differences in CD4+ T cells, CCL5, IL-17A and RANKL expression between the two age groups. CONCLUSIONS: SPF mice induced an age-related increase in CD4+ T cells co- expressed with IL-17A and RANKL, with occurring alveolar bone loss. In contrast, GF mice did not show age-related changes in CD4+ T cell migration and cytokine expression.

Hyperlipidemia is involved in apoptosis in rat submandibular glands.

OBJECTIVE: The aim of the present study was to investigate the effects of hyperlipidemia on histological changes and apoptosis in submandibular glands using apolipoprotein E (apoE)-deficient rats. DESIGN: Histopathological findings related to induced apoptosis in the submandibular glands were compared between apoE-deficient rats (n=6; male; age, 16 weeks) and the corresponding wild-type rats (n=6). RESULTS: ApoE-deficient rats showed significantly higher plasma levels of oxidized low-density lipoprotein (LDL), total cholesterol, very LDL and LDL, and lower plasma levels of high-density lipoprotein when compared to control rats (P<0.05). Lipid deposition in the submandibular gland was observed in apoE-deficient rat group and in none of the control group. Significant increases in vacuolization and apoptosis in acinar cells were observed in apoE-deficient rats, as compared to control rats (P<0.05). The number of active caspase-3-positive cells was also higher in the apoE-deficient rat group when compared with the control group (P<0.01). CONCLUSIONS: According to our results, hyperlipidemia induced apoptosis in apoE-deficient rat submandibular glands. Oxidized LDL generation in case of hyperlipidemia may trigger off a reaction of apoptotic acinar cells with vacuolization in the submandibular glands.

Is there an occupational status gradient in the development of periodontal disease in Japanese workers? A 5-year prospective cohort study.

BACKGROUND: Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. METHODS: In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. RESULTS: Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. CONCLUSIONS: We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population.

Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet.

Obesity induces gingival oxidative stress, which is involved in the progression of alveolar bone resorption. The antioxidant effect of hydrogen-rich water may attenuate gingival oxidative stress and prevent alveolar bone resorption in cases of obesity. We examined whether hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption in obese rats fed a high-fat diet. Male Fischer 344 rats (n = 18) were divided into three groups of six rats each: a control group (fed a regular diet and drinking distilled water) and two experimental groups (fed a high-fat diet and drinking distilled water or hydrogen-rich water). The level of 8-hydroxydeoxyguanosine was determined to evaluate oxidative stress. The bone mineral density of the alveolar bone was analyzed by micro-computerized tomography. Obese rats, induced by a high-fat diet, showed a higher gingival level of 8-hydroxydeoxyguanosine and a lower level of alveolar bone density compared to the control group. Drinking hydrogen-rich water suppressed body weight gain, lowered gingival level of 8-hydroxydeoxyguanosine, and reduced alveolar bone resorption in rats on a high-fat diet. The results indicate that hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption by limiting obesity.

Visualization of Oxidative Stress Induced by Experimental Periodontitis in Keap1-Dependent Oxidative Stress Detector-Luciferase Mice.

The aim of this study was to investigate whether a Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mouse model would be useful for the visualization of oxidative stress induced by experimental periodontitis. A ligature was placed around the mandibular first molars for seven days to induce periodontitis. Luciferase activity was measured with an intraperitoneal injection of d-luciferin on days 0, 1, and 7. The luciferase activity in the periodontitis group was significantly greater than that in the control group at seven days. The expressions of heme oxygenase-1 (HO-1) and malondialdehyde in periodontal tissue were significantly higher in the periodontitis group than in the control group. Immunofluorescent analysis confirmed that the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) occurred more frequently in the periodontitis group than in the control group. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the OKD-LUC model. Thus, the OKD-LUC mouse model may be useful for exploring the mechanism underlying the relationship between the Nrf2/antioxidant defense pathway and periodontitis by enabling the visualization of oxidative stress over time.