Journal of Dental Research最新文献

{"title":"Photobiomodulation of Gingival Cells Challenged with Viable Oral Microbes","authors":"J. Tanum, H.E. Kim, S.M. Lee, A. Kim, J. Korostoff, G. Hwang","doi":"10.1177/00220345241246529","DOIUrl":"https://doi.org/10.1177/00220345241246529","url":null,"abstract":"The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs’ response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment","authors":"X. Zhao, D. Leng, H. Wang, H. Jin, Y. Wu, Z. Qin, D. Wu, X. Wei","doi":"10.1177/00220345241238154","DOIUrl":"https://doi.org/10.1177/00220345241238154","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O<jats:sub>2</jats:sub> in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis","authors":"R.Y. Ma, Z.L. Deng, Q.Y. Du, M.Q. Dai, Y.Y. Luo, Y.E. Liang, X.Z. Dai, S.M. Guo, W.H. Zhao","doi":"10.1177/00220345241230867","DOIUrl":"https://doi.org/10.1177/00220345241230867","url":null,"abstract":"Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Orthodontics: Critical Review","authors":"N.F. Nordblom, M. Büttner, F. Schwendicke","doi":"10.1177/00220345241235606","DOIUrl":"https://doi.org/10.1177/00220345241235606","url":null,"abstract":"With increasing digitalization in orthodontics, certain orthodontic manufacturing processes such as the fabrication of indirect bonding trays, aligner production, or wire bending can be automated. However, orthodontic treatment planning and evaluation remains a specialist’s task and responsibility. As the prediction of growth in orthodontic patients and response to orthodontic treatment is inherently complex and individual, orthodontists make use of features gathered from longitudinal, multimodal, and standardized orthodontic data sets. Currently, these data sets are used by the orthodontist to make informed, rule-based treatment decisions. In research, artificial intelligence (AI) has been successfully applied to assist orthodontists with the extraction of relevant data from such data sets. Here, AI has been applied for the analysis of clinical imagery, such as automated landmark detection in lateral cephalograms but also for evaluation of intraoral scans or photographic data. Furthermore, AI is applied to help orthodontists with decision support for treatment decisions such as the need for orthognathic surgery or for orthodontic tooth extractions. One major challenge in current AI research in orthodontics is the limited generalizability, as most studies use unicentric data with high risks of bias. Moreover, comparing AI across different studies and tasks is virtually impossible as both outcomes and outcome metrics vary widely, and underlying data sets are not standardized. Notably, only few AI applications in orthodontics have reached full clinical maturity and regulatory approval, and researchers in the field are tasked with tackling real-world evaluation and implementation of AI into the orthodontic workflow.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Mechanism of MSCs Responding to Occlusal Force for Bone Homeostasis","authors":"F. Wang, H. Wang, H. Zhang, B. Sun, Z. Wang","doi":"10.1177/00220345241236120","DOIUrl":"https://doi.org/10.1177/00220345241236120","url":null,"abstract":"Alveolar bone, as tooth-supporting bone for mastication, is sensitive to occlusal force. However, the mechanism of alveolar bone loss after losing occlusal force remains unclear. Here, we performed single-cell RNA sequencing of nonhematopoietic (CD45<jats:sup>–</jats:sup>) cells in mouse alveolar bone after removing the occlusal force. Mesenchymal stromal cells (MSCs) and endothelial cell (EC) subsets were significantly decreased in frequency, as confirmed by immunofluorescence and flow cytometry. The osteogenic and proangiogenic abilities of MSCs were impaired, and the expression of mechanotransducers yes associated protein 1 ( Yap) and WW domain containing transcription regulator 1 ( Taz) in MSCs decreased. Conditional deletion of Yap and Taz from LepR<jats:sup>+</jats:sup> cells, which are enriched in MSCs that are important for adult bone homeostasis, significantly decreased alveolar bone mass and resisted any further changes in bone mass induced by occlusal force changes. Interestingly, LepR-Cre; Yap<jats:sup>f/f</jats:sup>; Taz<jats:sup>f/f</jats:sup> mice showed a decrease in CD31<jats:sup>hi</jats:sup> endomucin (Emcn)<jats:sup>hi</jats:sup> endothelium, and the expression of some EC-derived signals acting on osteoblastic cells was inhibited in alveolar bone. Mechanistically, conditional deletion of Yap and Taz in LepR<jats:sup>+</jats:sup> cells inhibited the secretion of pleiotrophin (Ptn), which impaired the proangiogenic capacity of LepR<jats:sup>+</jats:sup> cells. Knockdown in MSC-derived Ptn repressed human umbilical vein EC tube formation in vitro. More important, administration of recombinant PTN locally recovered the frequency of CD31<jats:sup>hi</jats:sup>Emcn<jats:sup>hi</jats:sup> endothelium and rescued the low bone mass phenotype of LepR-Cre; Yap<jats:sup>f/f</jats:sup>; Taz<jats:sup>f/f</jats:sup> mice. Taken together, these findings suggest that occlusal force governs MSC-regulated endothelium to maintain alveolar bone homeostasis through the Yap/Taz/Ptn axis, providing a reference for further understanding of the relationship between dysfunction and bone homeostasis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tongue-Coating Microbial and Metabolic Characteristics in Halitosis","authors":"Y. Zhang, K.L. Lo, A.N. Liman, X.P. Feng, W. Ye","doi":"10.1177/00220345241230067","DOIUrl":"https://doi.org/10.1177/00220345241230067","url":null,"abstract":"Halitosis is a common oral condition, which leads to social embarrassment and affects quality of life. Cumulative evidence has suggested the association of tongue-coating microbiome with the development of intraoral halitosis. The dynamic variations of tongue-coating microbiota and metabolites in halitosis have not been fully elucidated. Therefore, the present study aimed to determine the tongue-coating microbial and metabolic characteristics in halitosis subjects without other oral diseases using metagenomics and metabolomics analysis. The participants underwent oral examination, halitosis assessment, and tongue-coating sample collection for the microbiome and metabolome analysis. It was found that the microbiota richness and diversity were significantly elevated in the halitosis group. Furthermore, species from Actinomyces, Prevotella, Veillonella, and Solobacterium were significantly more abundant in the halitosis group. However, the Rothia and Streptococcus species exhibited opposite tendencies. Eleven Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in the halitosis tongue coatings, including cysteine and methionine metabolism. Functional genes related to sulfur, indole, skatole, and cadaverine metabolic processes (such as serA, metH, metK and dsrAB) were identified to be more abundant in the halitosis samples. The metabolome analysis revealed that indole-3-acetic, ornithine, and L-tryptophan were significantly elevated in the halitosis samples. Furthermore, it was observed that the values of volatile sulfur compounds and indole-3-acetic abundances were positively correlated. The multiomics analysis identified the metagenomic and metabolomic characteristics to differentiate halitosis from healthy individuals using the least absolute shrinkage and selection operator logistic regression and random forest classifier. A total of 19 species and 39 metabolites were identified as features in halitosis patients, which included indole-3-acetic acid, Bacillus altitudinis, Candidatus Saccharibacteria, and Actinomyces species. In conclusion, an evident shift in microbiome and metabolome characteristics was observed in the halitosis tongue coating, which may have a potential etiological significance and provide novel insights into the mechanism for halitosis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke","authors":"J. Leskelä, J. Putaala, N. Martinez-Majander, L. Tulkki, M. Manzoor, S. Zaric, P. Ylikotila, R. Lautamäki, A. Saraste, S. Suihko, E. Könönen, J. Sinisalo, P.J. Pussinen, S. Paju","doi":"10.1177/00220345241232406","DOIUrl":"https://doi.org/10.1177/00220345241232406","url":null,"abstract":"Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls ( P &lt; 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18–34.5) and severe periodontitis with an OR of 7.48 (1.24–44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87–23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01–6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72–40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Evolution of Developing Palate in Mice","authors":"B. Wang, Z. Zhang, J. Zhao, Y. Ma, Y. Wang, N. Yin, T. Song","doi":"10.1177/00220345241232317","DOIUrl":"https://doi.org/10.1177/00220345241232317","url":null,"abstract":"The intricate formation of the palate involves a series of complex events, yet its mechanistic basis remains uncertain. To explore major cell populations in the palate and their roles during development, we constructed a spatiotemporal transcription landscape of palatal cells. Palate samples from C57BL/6 J mice at embryonic days 12.5 (E12.5), 14.5 (E14.5), and 16.5 (E16.5) underwent single-cell RNA sequencing (scRNA-seq) to identify distinct cell subsets. In addition, spatial enhanced resolution omics-sequencing (stereo-seq) was used to characterize the spatial distribution of these subsets. Integrating scRNA-seq and stereo-seq with CellTrek annotated mesenchymal and epithelial cellular components of the palate during development. Furthermore, cellular communication networks between these cell subpopulations were analyzed to discover intercellular signaling during palate development. From the analysis of the middle palate, both mesenchymal and epithelial populations were spatially segregated into 3 domains. The middle palate mesenchymal subpopulations were associated with tooth formation, ossification, and tissue remodeling, with initial state cell populations located proximal to the dental lamina. The nasal epithelium of the palatal shelf exhibited richer humoral immune responses than the oral side. Specific enrichment of Tgfβ3 and Pthlh signals in the midline epithelial seam at E14.5 suggested a role in epithelial–mesenchymal transition. In summary, this study provides high-resolution transcriptomic information, contributing to a deeper mechanistic understanding of palate biology and pathophysiology.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for Improving Impaired Osseointegration in Compromised Animal Models","authors":"J. Deng, C. Van Duyn, D. J. Cohen, Z. Schwartz, B. D. Boyan","doi":"10.1177/00220345241231777","DOIUrl":"https://doi.org/10.1177/00220345241231777","url":null,"abstract":"Implant osseointegration is reduced in patients with systemic conditions that compromise bone quality, such as osteoporosis, disuse syndrome, and type 2 diabetes. Studies using rodent models designed to mimic these compromised conditions demonstrated reduced bone-to-implant contact (BIC) or a decline in bone mineral density. These adverse effects are a consequence of disrupted intercellular communication. A variety of approaches have been developed to compensate for the altered microenvironment inherent in compromised conditions, including the use of biologics and implant surface modification. Chemical and physical modification of surface properties at the microscale, mesoscale, and nanoscale levels to closely resemble the surface topography of osteoclast resorption pits found in bone has proven to be a highly effective strategy for improving implant osseointegration. The addition of hydrophilicity to the surface further enhances osteoblast response at the bone-implant interface. These surface modifications, applied either alone or in combination, improve osseointegration by increasing proliferation and osteoblastic differentiation of osteoprogenitor cells and enhancing angiogenesis while modulating osteoclast activity to achieve net new bone formation, although the specific effects vary with surface treatment. In addition to direct effects on surface-attached cells, the communication between bone marrow stromal cells and immunomodulatory cells is sensitive to these surface properties. This article reports on the advances in titanium surface modifications, alone and in combination with novel therapeutics in animal models of human disease affecting bone quality. It offers clinically translatable perspectives for clinicians to consider when using different surface modification strategies to improve long-term implant performance in compromised patients. This review supports the use of surface modifications, bioactive coatings, and localized therapeutics as pragmatic approaches to improve BIC and enhance osteogenic activity from both structural and molecular standpoints.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Alcohol Harm Paradox in Periodontitis","authors":"L.M. Oliveira, F.B. Zanatta, S.A. Costa, T.R. Pelissari, S.E. Baumeister, F.F. Demarco, G.G. Nascimento","doi":"10.1177/00220345241235614","DOIUrl":"https://doi.org/10.1177/00220345241235614","url":null,"abstract":"Individuals of lower socioeconomic position (SEP) experience a greater rate of alcohol-related harms, yet they consume equal or lower amounts of alcohol than higher-SEP individuals. This phenomenon, called the “alcohol harm paradox” (AHP), gained attention recently, and different mechanisms have been proposed to explain it. Since both SEP and alcohol have been suggested to be associated with periodontitis risk, we conducted a secondary analysis using data from the National Health and Nutrition Examination Survey 2011 to 2012 and 2013 to 2014 cycles, aiming to examine 1) whether the association between alcohol consumption and periodontitis is modified by SEP and 2) the extent to which the effect of SEP inequalities on periodontitis is mediated by and/or interacts with alcohol consumption. We set educational attainment as the main SEP proxy and tested the poverty income ratio in subsequent sensitivity analyses. Effect measure modification analysis was employed, considering heavy drinking as exposure, and causal mediation analysis based on the potential outcome’s framework decomposed the effect of SEP on periodontitis in proportions attributable to mediation and interaction. Models were fitted using binary logistic regression and adjusted for sex, ethnicity, age, body mass index, smoking status, diabetes, binge drinking, and regular preventive dental visits. The analytical sample comprised 4,057 participants. After adjusting for covariates, less educated heavy drinkers presented 175% (odds ratio, 2.75; 95% confidence interval [CI], 2.04–3.72) higher odds of periodontitis than their counterparts, and super-additive associations were found (relative excess risk due to interaction: 1.35; 95% CI, 0.49–2.20). Additionally, −69.5% (95% CI, −122.1% to −16.8%) of the effects of education on periodontitis were attributable to interaction with heavy drinking, consistent with the AHP. No contribution was found for the mechanism of mediation. Heavy drinking disproportionately impacts the occurrence of periodontitis in lower-SEP individuals. Lower-SEP individuals seem to experience differential effects of heavy drinking on periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}