Pub Date : 2025-10-22DOI: 10.1177/00220345251384633
M Mohammadi,J Holmer,H Imberg,H Albrektsson,M Eriksdotter,K Buhlin
Risk factors for dementia include cardiovascular disease, smoking, and diabetes, which also are linked to compromised oral health and periodontal disease. Tooth loss, the hallmark of compromised oral health, is of interest for its systemic effects, including potential impacts on cognitive function. To evaluate tooth loss as a prognostic indicator in dementia, we conducted a register-based cohort study to assess associations of compromised oral health, defined by tooth loss, with mortality risk and progression of cognitive decline. The study population, obtained from linked Swedish nationwide health and quality assurance registries, comprised 3,361 individuals diagnosed with dementia from 2010 to 2013, with follow-up until 2018. Participants were categorized by tooth count: severe tooth loss (<10 remaining teeth), moderate tooth loss (10 to 19 remaining teeth), and a reference group with ≥20 remaining teeth. Mortality rate was analysed by Cox and Poisson regression models, and cognitive decline was assessed by longitudinal analyses of Mini Mental State Examination scores. Analyses were adjusted for demographic and health variables. Tooth loss at the time of dementia diagnosis was not independently associated with increased mortality after covariate adjustment (hazard ratio, 1.12 [95% CI, 0.97 to 1.28] for severe tooth loss vs reference). Annual Mini Mental State Examination scores declined across all groups, with no statistically significant differences among groups. After robust covariate control, no association was observed between tooth loss and increased mortality or cognitive decline in individuals newly diagnosed with dementia. Further studies are needed to determine whether tooth loss is an independent risk factor or a contributing marker in dementia prognosis.
{"title":"Tooth Loss in Individuals with Dementia: A Swedish Register-Based Cohort Study.","authors":"M Mohammadi,J Holmer,H Imberg,H Albrektsson,M Eriksdotter,K Buhlin","doi":"10.1177/00220345251384633","DOIUrl":"https://doi.org/10.1177/00220345251384633","url":null,"abstract":"Risk factors for dementia include cardiovascular disease, smoking, and diabetes, which also are linked to compromised oral health and periodontal disease. Tooth loss, the hallmark of compromised oral health, is of interest for its systemic effects, including potential impacts on cognitive function. To evaluate tooth loss as a prognostic indicator in dementia, we conducted a register-based cohort study to assess associations of compromised oral health, defined by tooth loss, with mortality risk and progression of cognitive decline. The study population, obtained from linked Swedish nationwide health and quality assurance registries, comprised 3,361 individuals diagnosed with dementia from 2010 to 2013, with follow-up until 2018. Participants were categorized by tooth count: severe tooth loss (<10 remaining teeth), moderate tooth loss (10 to 19 remaining teeth), and a reference group with ≥20 remaining teeth. Mortality rate was analysed by Cox and Poisson regression models, and cognitive decline was assessed by longitudinal analyses of Mini Mental State Examination scores. Analyses were adjusted for demographic and health variables. Tooth loss at the time of dementia diagnosis was not independently associated with increased mortality after covariate adjustment (hazard ratio, 1.12 [95% CI, 0.97 to 1.28] for severe tooth loss vs reference). Annual Mini Mental State Examination scores declined across all groups, with no statistically significant differences among groups. After robust covariate control, no association was observed between tooth loss and increased mortality or cognitive decline in individuals newly diagnosed with dementia. Further studies are needed to determine whether tooth loss is an independent risk factor or a contributing marker in dementia prognosis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"244 1","pages":"220345251384633"},"PeriodicalIF":7.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338834","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}
Pub Date : 2025-10-22DOI: 10.1177/00220345251380210
K Prasongyuenyong,W S Kim,Z Chen,K I Ko
Fibroblasts are the principal mesenchymal cell type found within the connective tissues of all organs. Once thought to play a passive role in tissue remodeling, fibroblasts have now emerged as a key player in regulating structural immunity and modulating the reparative injury response. A recent surge in single-cell RNA sequencing studies has advanced our understanding of the biology of fibroblasts, highlighting their cellular diversity and organization across health and diseased conditions at an unprecedented resolution. In this review, we discuss up-to-date literature on fibroblast subpopulations identified from 2 distinct barrier tissues: oral mucosa and skin. We focus on the transcriptomic signatures that distinguish subsets of fibroblasts in homeostasis and perturbed conditions (i.e., wound healing or chronic inflammatory diseases), and we link them to mechanistic studies that provide functional insights. A deeper understanding of fibroblast diversity and its functional significance may uncover tissue-specific roles in regeneration and immunomodulation, which will be crucial for the development of precision therapy that directly targets fibroblast subsets.
{"title":"Single-Cell Analysis of Fibroblast Subpopulations in Skin and Oral Mucosa.","authors":"K Prasongyuenyong,W S Kim,Z Chen,K I Ko","doi":"10.1177/00220345251380210","DOIUrl":"https://doi.org/10.1177/00220345251380210","url":null,"abstract":"Fibroblasts are the principal mesenchymal cell type found within the connective tissues of all organs. Once thought to play a passive role in tissue remodeling, fibroblasts have now emerged as a key player in regulating structural immunity and modulating the reparative injury response. A recent surge in single-cell RNA sequencing studies has advanced our understanding of the biology of fibroblasts, highlighting their cellular diversity and organization across health and diseased conditions at an unprecedented resolution. In this review, we discuss up-to-date literature on fibroblast subpopulations identified from 2 distinct barrier tissues: oral mucosa and skin. We focus on the transcriptomic signatures that distinguish subsets of fibroblasts in homeostasis and perturbed conditions (i.e., wound healing or chronic inflammatory diseases), and we link them to mechanistic studies that provide functional insights. A deeper understanding of fibroblast diversity and its functional significance may uncover tissue-specific roles in regeneration and immunomodulation, which will be crucial for the development of precision therapy that directly targets fibroblast subsets.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"139 1","pages":"220345251380210"},"PeriodicalIF":7.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338825","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}
Pub Date : 2025-10-18DOI: 10.1177/00220345251372506
H Mortazavi,R Said,G S Katselis,P Chumala,G Pannone,S Papagerakis,P Papagerakis
Several empirical observations strongly suggest that salivary function is regulated by the circadian clock. Salivary volume, electrolytes levels, and saliva protein composition all show 24-h cycle fluctuations. The exact effects of circadian disruption on salivary gland (SG) physiology and its potential role in salivary pathologies have not been elucidated. Here, we examined the effects of circadian disruption on SG structure, functional gene and protein expression, and immune status using several circadian knockout (KO) mice models where we targeted the following canonical clock genes: brain and muscle ARNT-like 1 protein (Bmal1) KO, Period2 (Per2) KO, Cryptochrome1 (Cry1) KO, Cryptochrome2 (Cry2) KO, and Cryptochrome 1 and 2 double KO (DKOCry). All mice were females of young and old age, and data were compared with wild type (control) mice. Our results showed that circadian dysregulation had limited effects on stimulated salivary secretion and SG structure. Yet, circadian disruption significantly affected the expression of several key salivary markers, including mucins, amylase, and aquaporins, in young and aged SGs with increased amylase and acidic mucin production observed in several KO models. In addition, targeting of clock genes has resulted in subtle alterations of the salivary immune microenvironment with increased lymphocyte infiltration and upregulated levels of proinflammatory cytokines. These immune shifts were more pronounced in aged glands with the most proinflammatory phenotypes observed in DKOCry and Bmal1KO mice. Collectively, our results implicate the circadian clock in the intricate temporal regulation governing SG function. Our data also suggest that circadian dysregulation may predispose to increased tissue stress and inflammation. Exploration of salivary system chronobiology represents a new avenue for salivary disease prevention and treatment.
{"title":"Effects of Circadian Misalignment on Young and Aging Salivary Glands.","authors":"H Mortazavi,R Said,G S Katselis,P Chumala,G Pannone,S Papagerakis,P Papagerakis","doi":"10.1177/00220345251372506","DOIUrl":"https://doi.org/10.1177/00220345251372506","url":null,"abstract":"Several empirical observations strongly suggest that salivary function is regulated by the circadian clock. Salivary volume, electrolytes levels, and saliva protein composition all show 24-h cycle fluctuations. The exact effects of circadian disruption on salivary gland (SG) physiology and its potential role in salivary pathologies have not been elucidated. Here, we examined the effects of circadian disruption on SG structure, functional gene and protein expression, and immune status using several circadian knockout (KO) mice models where we targeted the following canonical clock genes: brain and muscle ARNT-like 1 protein (Bmal1) KO, Period2 (Per2) KO, Cryptochrome1 (Cry1) KO, Cryptochrome2 (Cry2) KO, and Cryptochrome 1 and 2 double KO (DKOCry). All mice were females of young and old age, and data were compared with wild type (control) mice. Our results showed that circadian dysregulation had limited effects on stimulated salivary secretion and SG structure. Yet, circadian disruption significantly affected the expression of several key salivary markers, including mucins, amylase, and aquaporins, in young and aged SGs with increased amylase and acidic mucin production observed in several KO models. In addition, targeting of clock genes has resulted in subtle alterations of the salivary immune microenvironment with increased lymphocyte infiltration and upregulated levels of proinflammatory cytokines. These immune shifts were more pronounced in aged glands with the most proinflammatory phenotypes observed in DKOCry and Bmal1KO mice. Collectively, our results implicate the circadian clock in the intricate temporal regulation governing SG function. Our data also suggest that circadian dysregulation may predispose to increased tissue stress and inflammation. Exploration of salivary system chronobiology represents a new avenue for salivary disease prevention and treatment.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"28 1","pages":"220345251372506"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311477","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}
Lipopolysaccharide (LPS) is a virulence factor of gram-negative bacteria, and endotoxemia or translocation of LPS in serum plays a significant role in oral and systemic pathologies. The contribution of the oral microbiome composition to saliva LPS activity and endotoxemia remains unclear. We investigated whether salivary and serum LPS levels are associated with oral microbiome diversity, taxonomic profiles, and functional characteristics. The oral microbiome was analyzed using metagenomic sequencing of saliva from 298 individuals enrolled in a multicenter case-control study, SECRETO (NCT01934725). Serum and salivary LPS activities were measured, and multiple linear regression models were fitted to identify the microbial taxa that predicted LPS levels. MaAsLin2 (Microbiome Multivariable Associations with Linear Models) was used to determine the associations of microbial functional features and LPS levels. Salivary alpha diversity was positively associated with serum LPS but negatively associated with salivary LPS, smoking, and antibiotic use in the preceding 1 to 6 mo. Community composition (beta diversity) differed between the salivary LPS tertiles (P = 0.001) but not between serum LPS tertiles. In total, 10 oral taxa associated with serum LPS tertiles and 59 with salivary LPS tertiles were identified. Prevotella, Neisseria, Leptotrichia, and Porphyromonas had significant positive associations with salivary LPS, whereas Fusobacterium had a negative association. Among these genera, Prevotella sp. E13_17, P. gingivalis, L. wadei, and F. nucleatum were the species with the strongest associations. Among the 1,016 oral microbiome metabolic features, several were linked to the biosynthesis of LPS, lipid A, and O-antigen pathways. The oral microbiome composition was strongly associated with salivary LPS activity in addition to weaker links to serum LPS. Oral microbiota-derived LPS activity in saliva was associated with microbial metabolism characterized by the predominance of proliferation and biosynthesis pathways. Our study indicates that dysbiosis of the oral microbiome is a source of increased salivary and serum LPS activity.
{"title":"Oral Microbial Determinants of Saliva and Serum Lipopolysaccharide Activity.","authors":"M Manzoor,J Putaala,S Zaric,J Leskelä,A Dong,E Könönen,L Lahti,S Paju,P J Pussinen","doi":"10.1177/00220345251370995","DOIUrl":"https://doi.org/10.1177/00220345251370995","url":null,"abstract":"Lipopolysaccharide (LPS) is a virulence factor of gram-negative bacteria, and endotoxemia or translocation of LPS in serum plays a significant role in oral and systemic pathologies. The contribution of the oral microbiome composition to saliva LPS activity and endotoxemia remains unclear. We investigated whether salivary and serum LPS levels are associated with oral microbiome diversity, taxonomic profiles, and functional characteristics. The oral microbiome was analyzed using metagenomic sequencing of saliva from 298 individuals enrolled in a multicenter case-control study, SECRETO (NCT01934725). Serum and salivary LPS activities were measured, and multiple linear regression models were fitted to identify the microbial taxa that predicted LPS levels. MaAsLin2 (Microbiome Multivariable Associations with Linear Models) was used to determine the associations of microbial functional features and LPS levels. Salivary alpha diversity was positively associated with serum LPS but negatively associated with salivary LPS, smoking, and antibiotic use in the preceding 1 to 6 mo. Community composition (beta diversity) differed between the salivary LPS tertiles (P = 0.001) but not between serum LPS tertiles. In total, 10 oral taxa associated with serum LPS tertiles and 59 with salivary LPS tertiles were identified. Prevotella, Neisseria, Leptotrichia, and Porphyromonas had significant positive associations with salivary LPS, whereas Fusobacterium had a negative association. Among these genera, Prevotella sp. E13_17, P. gingivalis, L. wadei, and F. nucleatum were the species with the strongest associations. Among the 1,016 oral microbiome metabolic features, several were linked to the biosynthesis of LPS, lipid A, and O-antigen pathways. The oral microbiome composition was strongly associated with salivary LPS activity in addition to weaker links to serum LPS. Oral microbiota-derived LPS activity in saliva was associated with microbial metabolism characterized by the predominance of proliferation and biosynthesis pathways. Our study indicates that dysbiosis of the oral microbiome is a source of increased salivary and serum LPS activity.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"19 1","pages":"220345251370995"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311480","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}
Pub Date : 2025-10-18DOI: 10.1177/00220345251376295
P. Chen, M.C. Embree, M.-K. Chung, B.A. Winkelstein, E.J. Granquist, J.S. Lee, H. Yao
The temporomandibular joint (TMJ) features unique tissue structures that support its complex functional demands. Alterations in these structures are often linked to jaw dysfunction, with pain being one of the most prevalent symptoms. However, the mechanisms underlying TMJ pain and its relationship with structural deterioration or functional impairment remain poorly understood. A comprehensive understanding of the interplay among TMJ structure, function, and pain is essential for uncovering disease mechanisms and developing effective therapies. To date, TMJ research in humans and animal models has been predominantly conducted in separate domains of structure, function, and pain, limiting integrative insights. Clinical studies also show inconsistent correlations among joint structural changes, jaw dysfunctions, and craniofacial pain, complicating diagnosis and treatments. This review aims to bridge these traditionally fragmented areas by synthesizing current knowledge across macroscopic and microscopic scales in human and animal models. TMJ diseases involve spatially proximate cellular, extracellular, and neural components that undergo multiscale spatiotemporal changes. These components experience complex mechanical loading during joint movement, triggering mechanical, neural, and immune responses that interact bidirectionally to influence TMJ integrity and pain. In turn, the brain modulates motor output and autonomic function, further affecting joint mechanics and cellular and nociceptive responses. To holistically and quantitatively assess these spatiotemporal dynamic processes, we propose a multiscale and multiphysics framework that integrates joint and tissue biomechanics, biochemical signals, cellular responses, nociception, and psychosocial influences. Realizing this vision requires a transdisciplinary effort and the development and adaptation of advanced methods to study TMJ at unprecedented resolution and details. By unifying structural, functional, and pain-related data, this integrated multiscale approach holds promise for elucidating new mechanisms of TMJ development, disease onset and progression, and pain chronicity. Ultimately, it may guide more effective diagnostics and treatments, including the combined use of physical therapy, neuromodulation, and biologically targeted interventions.
{"title":"Bridging Temporomandibular Joint Structure, Function, and Pain: An Integrated Multiscale Perspective","authors":"P. Chen, M.C. Embree, M.-K. Chung, B.A. Winkelstein, E.J. Granquist, J.S. Lee, H. Yao","doi":"10.1177/00220345251376295","DOIUrl":"https://doi.org/10.1177/00220345251376295","url":null,"abstract":"The temporomandibular joint (TMJ) features unique tissue structures that support its complex functional demands. Alterations in these structures are often linked to jaw dysfunction, with pain being one of the most prevalent symptoms. However, the mechanisms underlying TMJ pain and its relationship with structural deterioration or functional impairment remain poorly understood. A comprehensive understanding of the interplay among TMJ structure, function, and pain is essential for uncovering disease mechanisms and developing effective therapies. To date, TMJ research in humans and animal models has been predominantly conducted in separate domains of structure, function, and pain, limiting integrative insights. Clinical studies also show inconsistent correlations among joint structural changes, jaw dysfunctions, and craniofacial pain, complicating diagnosis and treatments. This review aims to bridge these traditionally fragmented areas by synthesizing current knowledge across macroscopic and microscopic scales in human and animal models. TMJ diseases involve spatially proximate cellular, extracellular, and neural components that undergo multiscale spatiotemporal changes. These components experience complex mechanical loading during joint movement, triggering mechanical, neural, and immune responses that interact bidirectionally to influence TMJ integrity and pain. In turn, the brain modulates motor output and autonomic function, further affecting joint mechanics and cellular and nociceptive responses. To holistically and quantitatively assess these spatiotemporal dynamic processes, we propose a multiscale and multiphysics framework that integrates joint and tissue biomechanics, biochemical signals, cellular responses, nociception, and psychosocial influences. Realizing this vision requires a transdisciplinary effort and the development and adaptation of advanced methods to study TMJ at unprecedented resolution and details. By unifying structural, functional, and pain-related data, this integrated multiscale approach holds promise for elucidating new mechanisms of TMJ development, disease onset and progression, and pain chronicity. Ultimately, it may guide more effective diagnostics and treatments, including the combined use of physical therapy, neuromodulation, and biologically targeted interventions.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"13 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310759","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}
Aging is a systemic immunomodulatory condition that makes organisms more susceptible to infection-driven periodontitis and associated periodontal tissue loss. Therefore, modulation of the bacterial-induced inflammatory host response could potentially target the pathophysiological systemic and local crosstalk and resulting tissue homeostasis in aged organisms. However, underlying pathways connecting nutritional modulation with periodontal disease pathology and whether an aged organism benefits from specific immunomodulatory nutritional components are not known. Based on its potent immunomodulatory function, we determined whether nutritional interventions with dietary monounsaturated fatty acid (FA) oleic acid (OA [C18:1]), a main component of Mediterranean-style diets, as compared with a Western-style diet component saturated FA palmitic acid (PA [C16:0]) could modify the response to periodontal infection in a murine periodontal Porphyromonas gingivalis-inoculation model comparing old (final age of up to 2 y) and young (21 wk) mice. Local fibroblastic response and circulating regulatory immune-competent lipid mediators (LMs) were determined to provide insights into underlying pathways and how diet and age affect inflammation and resolution of the periodontal infection. The dietary intake of PA enhances periodontal bone destruction in response to P. gingivalis infection in old mice, whereas an OA-enriched diet (ED) has a protective effect. Specifically, PA-ED enhances the inflammatory profile of the periodontal microenvironment and primes gingival fibroblasts, prominent regulators within local tissue homeostasis, toward an inflammatory phenotype. Moreover, systems-wide serological lipidomic analyses of LMs and their respective stimulation of osteoclast differentiation revealed 10-hydroxydocosahexaenoic acid, associated with OA intake, as a protective candidate for age- and nutrition-dependent regulation of osteoclast-driven bone loss. Given the rising prevalence of periodontitis in the aging population, incorporating OA-rich foods could offer promising strategies for addressing the sequelae of aging and promoting periodontal health.
{"title":"Fighting Age-Associated Bone Loss in Periodontitis with Dietary Interventions.","authors":"A Döding,A Petzold,O Ciaston,M Wichmann-Costaganna,P Schädel,J Symmank,H Noels,C Jacobs,K Becker,O Werz,U Schulze-Späte","doi":"10.1177/00220345251369518","DOIUrl":"https://doi.org/10.1177/00220345251369518","url":null,"abstract":"Aging is a systemic immunomodulatory condition that makes organisms more susceptible to infection-driven periodontitis and associated periodontal tissue loss. Therefore, modulation of the bacterial-induced inflammatory host response could potentially target the pathophysiological systemic and local crosstalk and resulting tissue homeostasis in aged organisms. However, underlying pathways connecting nutritional modulation with periodontal disease pathology and whether an aged organism benefits from specific immunomodulatory nutritional components are not known. Based on its potent immunomodulatory function, we determined whether nutritional interventions with dietary monounsaturated fatty acid (FA) oleic acid (OA [C18:1]), a main component of Mediterranean-style diets, as compared with a Western-style diet component saturated FA palmitic acid (PA [C16:0]) could modify the response to periodontal infection in a murine periodontal Porphyromonas gingivalis-inoculation model comparing old (final age of up to 2 y) and young (21 wk) mice. Local fibroblastic response and circulating regulatory immune-competent lipid mediators (LMs) were determined to provide insights into underlying pathways and how diet and age affect inflammation and resolution of the periodontal infection. The dietary intake of PA enhances periodontal bone destruction in response to P. gingivalis infection in old mice, whereas an OA-enriched diet (ED) has a protective effect. Specifically, PA-ED enhances the inflammatory profile of the periodontal microenvironment and primes gingival fibroblasts, prominent regulators within local tissue homeostasis, toward an inflammatory phenotype. Moreover, systems-wide serological lipidomic analyses of LMs and their respective stimulation of osteoclast differentiation revealed 10-hydroxydocosahexaenoic acid, associated with OA intake, as a protective candidate for age- and nutrition-dependent regulation of osteoclast-driven bone loss. Given the rising prevalence of periodontitis in the aging population, incorporating OA-rich foods could offer promising strategies for addressing the sequelae of aging and promoting periodontal health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"39 1","pages":"220345251369518"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311441","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}
Dental caries is closely associated with microbiome dysbiosis. Incorporating antimicrobial agents can enhance the efficacy of fluoride toothpaste. Our previous studies showed that caffeic acid phenethyl ester (CAPE), derived from propolis, effectively inhibited cariogenic bacteria. To formulate a novel CAPE-containing fluoridated toothpaste and establish a multistage evaluation system assessing its caries-controlling efficacy. The CAPE toothpaste’s physicochemical properties were characterized. Its in vitro antimicrobial activity against Streptococcus mutans was examined using quantitative suspension and checkerboard microdilution assays. In vivo anticaries efficacy and biosafety were evaluated in a rat caries model ( n = 9/group) comparing 5 groups: untreated control (group NC), base toothpaste without CAPE (group B, 600 ppm F − ), CAPE–fluoride toothpaste (group C, 0.16 mg/mL CAPE + 600 ppm F − ), fluoride control (group F, DARLIE ® , 600 ppm F − ), and propolis nonfluoride control (group P, Red Seal ® ). Caries severity was scored using the Keyes method. Finally, in situ enamel repair ( n = 24 enamel blocks) and plaque microbiome modulation ( n = 6 samples) were assessed in a 7-d clinical study (ChiCTR2400089643) with 4 groups (groups NC, C, F, and P). The novel formulation showed stable physicochemical properties. Group C reduced S. mutans by 1.5-log10 within 3 min ( P = 0.0062 vs NC), and CAPE plus fluoride exhibited additive antibacterial properties (fractional inhibitory concentration index = 0.75). In rats, group C showed the lowest smooth-surface score (21.0 ± 1.7, P < 0.005 vs. all) and reduced sulcal lesion severity (slight dentinal lesions: P = 0.0181 vs. NC and P = 0.0318 vs. F). In situ, group C achieved 27.58% surface microhardness recovery ( P < 0.01 vs. all), with significant reductions in mineral loss and lesion depth ( P < 0.001 vs. all). Microbiome analysis revealed a preserved microbial diversity, increased Streptococcus oralis , and reduced cariogenic populations. The novel CAPE-containing fluoridated toothpaste effectively inhibited the onset and development of caries. Wider-ranging and longer-term clinical investigations are still needed.
{"title":"Caries Control by CAPE Toothpaste: In Vitro, In Vivo, and In Situ Analysis","authors":"Y.F. Wang, S.S. Dong, Y. Chen, Y.H. Zeng, Z.X. Chen, L.L. Zhang","doi":"10.1177/00220345251374959","DOIUrl":"https://doi.org/10.1177/00220345251374959","url":null,"abstract":"Dental caries is closely associated with microbiome dysbiosis. Incorporating antimicrobial agents can enhance the efficacy of fluoride toothpaste. Our previous studies showed that caffeic acid phenethyl ester (CAPE), derived from propolis, effectively inhibited cariogenic bacteria. To formulate a novel CAPE-containing fluoridated toothpaste and establish a multistage evaluation system assessing its caries-controlling efficacy. The CAPE toothpaste’s physicochemical properties were characterized. Its in vitro antimicrobial activity against <jats:italic toggle=\"yes\">Streptococcus mutans</jats:italic> was examined using quantitative suspension and checkerboard microdilution assays. In vivo anticaries efficacy and biosafety were evaluated in a rat caries model ( <jats:italic toggle=\"yes\">n</jats:italic> = 9/group) comparing 5 groups: untreated control (group NC), base toothpaste without CAPE (group B, 600 ppm F <jats:sup>−</jats:sup> ), CAPE–fluoride toothpaste (group C, 0.16 mg/mL CAPE + 600 ppm F <jats:sup>−</jats:sup> ), fluoride control (group F, DARLIE <jats:sup>®</jats:sup> , 600 ppm F <jats:sup>−</jats:sup> ), and propolis nonfluoride control (group P, Red Seal <jats:sup>®</jats:sup> ). Caries severity was scored using the Keyes method. Finally, in situ enamel repair ( <jats:italic toggle=\"yes\">n</jats:italic> = 24 enamel blocks) and plaque microbiome modulation ( <jats:italic toggle=\"yes\">n</jats:italic> = 6 samples) were assessed in a 7-d clinical study (ChiCTR2400089643) with 4 groups (groups NC, C, F, and P). The novel formulation showed stable physicochemical properties. Group C reduced <jats:italic toggle=\"yes\">S. mutans</jats:italic> by 1.5-log10 within 3 min ( <jats:italic toggle=\"yes\">P</jats:italic> = 0.0062 vs NC), and CAPE plus fluoride exhibited additive antibacterial properties (fractional inhibitory concentration index = 0.75). In rats, group C showed the lowest smooth-surface score (21.0 ± 1.7, <jats:italic toggle=\"yes\">P</jats:italic> < 0.005 vs. all) and reduced sulcal lesion severity (slight dentinal lesions: <jats:italic toggle=\"yes\">P</jats:italic> = 0.0181 vs. NC and <jats:italic toggle=\"yes\">P</jats:italic> = 0.0318 vs. F). In situ, group C achieved 27.58% surface microhardness recovery ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.01 vs. all), with significant reductions in mineral loss and lesion depth ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.001 vs. all). Microbiome analysis revealed a preserved microbial diversity, increased <jats:italic toggle=\"yes\">Streptococcus oralis</jats:italic> , and reduced cariogenic populations. The novel CAPE-containing fluoridated toothpaste effectively inhibited the onset and development of caries. Wider-ranging and longer-term clinical investigations are still needed.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310748","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}
Pub Date : 2025-10-18DOI: 10.1177/00220345251372909
R. Moffat, M.K.S. Charles-Ayinde, M. Fontana, X. Huang, S. Levy, S.L. Tomar, Y-H. Yu, E. Bell, K. Rwizi, C.H. Fox
Community water fluoridation (CWF) is a foundational public health intervention that has significantly reduced the global burden of dental caries across the lifespan. The American Association for Dental, Oral, and Craniofacial Research (AADOCR) reaffirms its strong support for CWF as a safe, evidence-based, and cost-saving method of delivering fluoride equitably to large populations. This updated position statement synthesizes nearly 8 decades of scientific literature, national surveillance data, and expert consensus to underscore the caries-preventive benefits of CWF and the role of fluoridation in reducing oral health disparities. AADOCR recommends the continued fluoridation of public water supplies at the optimal level of 0.7 mg/L and calls for sustained efforts in monitoring safety, improving public communication, and advancing research into fluoride’s impact on oral and systemic health.
{"title":"The AADOCR Position Statement on Community Water Fluoridation","authors":"R. Moffat, M.K.S. Charles-Ayinde, M. Fontana, X. Huang, S. Levy, S.L. Tomar, Y-H. Yu, E. Bell, K. Rwizi, C.H. Fox","doi":"10.1177/00220345251372909","DOIUrl":"https://doi.org/10.1177/00220345251372909","url":null,"abstract":"Community water fluoridation (CWF) is a foundational public health intervention that has significantly reduced the global burden of dental caries across the lifespan. The American Association for Dental, Oral, and Craniofacial Research (AADOCR) reaffirms its strong support for CWF as a safe, evidence-based, and cost-saving method of delivering fluoride equitably to large populations. This updated position statement synthesizes nearly 8 decades of scientific literature, national surveillance data, and expert consensus to underscore the caries-preventive benefits of CWF and the role of fluoridation in reducing oral health disparities. AADOCR recommends the continued fluoridation of public water supplies at the optimal level of 0.7 mg/L and calls for sustained efforts in monitoring safety, improving public communication, and advancing research into fluoride’s impact on oral and systemic health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"38 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311098","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}
Pub Date : 2025-10-18DOI: 10.1177/00220345251379764
S Trautmann,S Thangamurugan,C Fecher-Trost,J Dudek,V Flockerzi,V Helms,M Hannig
The dental pellicle is a continuously forming layer present at the interface between oral surfaces and saliva. It protects the dental surfaces by shielding against chemical and mechanical damages. The pellicle represents the basis for further biofilm development, and its formation starts after oral hygiene through the adsorption of mostly salivary proteins to all exposed oral surfaces. In spite of its important physiologic role, its formation process and composition are not yet revealed in all details. The objective of the current study was 1) to visualize and elucidate the individual proteomic composition of the very early (only a few seconds) formed in situ pellicle, named seconds-pellicle, and 2) to analyze changes in its ultrastructure and proteomic composition over time. Transmission electron microscopic analyses demonstrated the seconds-pellicle to consist of an already continuous electron-dense layer without a detectable increase in thickness within the first minutes of formation. Proteomic analyses showed it to consist of up to 841 proteins on an individual level, without elevating protein content or diversity over the first minutes. Analyses of several pellicle formation times enabled the detection of changes over time and the first direct verification of protein desorptions occurring during pellicle formation. Comparisons between the salivary and pellicle proteomes at the different formation times revealed insights in the amount of substance of single pellicle proteins over time. The present study provides first evidence that the pellicle forms instantaneously and dynamically on solid surfaces in the oral cavity. Furthermore, the data suggest these first proteins to be replaced by proteins adsorbing with higher selectivity to stabilize the pellicle within the first minutes of its formation. These insights represent the basis for selective modifications of the pellicle layer to control the originating biofilm and develop preventive strategies for oral biofilm management.
{"title":"Snapshot of the Seconds-Pellicle: Ultrastructure and Proteomic Changes.","authors":"S Trautmann,S Thangamurugan,C Fecher-Trost,J Dudek,V Flockerzi,V Helms,M Hannig","doi":"10.1177/00220345251379764","DOIUrl":"https://doi.org/10.1177/00220345251379764","url":null,"abstract":"The dental pellicle is a continuously forming layer present at the interface between oral surfaces and saliva. It protects the dental surfaces by shielding against chemical and mechanical damages. The pellicle represents the basis for further biofilm development, and its formation starts after oral hygiene through the adsorption of mostly salivary proteins to all exposed oral surfaces. In spite of its important physiologic role, its formation process and composition are not yet revealed in all details. The objective of the current study was 1) to visualize and elucidate the individual proteomic composition of the very early (only a few seconds) formed in situ pellicle, named seconds-pellicle, and 2) to analyze changes in its ultrastructure and proteomic composition over time. Transmission electron microscopic analyses demonstrated the seconds-pellicle to consist of an already continuous electron-dense layer without a detectable increase in thickness within the first minutes of formation. Proteomic analyses showed it to consist of up to 841 proteins on an individual level, without elevating protein content or diversity over the first minutes. Analyses of several pellicle formation times enabled the detection of changes over time and the first direct verification of protein desorptions occurring during pellicle formation. Comparisons between the salivary and pellicle proteomes at the different formation times revealed insights in the amount of substance of single pellicle proteins over time. The present study provides first evidence that the pellicle forms instantaneously and dynamically on solid surfaces in the oral cavity. Furthermore, the data suggest these first proteins to be replaced by proteins adsorbing with higher selectivity to stabilize the pellicle within the first minutes of its formation. These insights represent the basis for selective modifications of the pellicle layer to control the originating biofilm and develop preventive strategies for oral biofilm management.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"342 1","pages":"220345251379764"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311451","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}
Pub Date : 2025-10-18DOI: 10.1177/00220345251381633
S.H. Yang, Z.L. Tian, H.M. Wang, D. Sun, S.W. Qiao, Z.S. Shi, X. He, S. Zhu
Enhancing the durability of dentin bonding remains a significant challenge in dental restoration. This study introduces an innovative approach using aldehyde-grafted polyaspartate (PACA) to achieve spatiotemporal regulation of biomimetic mineralization through collagen cross-linking. The collagen cross-linking capability of PACA was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis. Its ability to induce intrafibrillar mineralization of collagen fibrils was investigated using a rat tail collagen model through dynamic light scattering, zeta potential measurements, and transmission electron microscopy. In addition, the remineralization efficacy of PACA on demineralized dentin collagen was evaluated using scanning electron microscopy, energy dispersive X-ray spectroscopy, and atomic force microscopy. These analyses revealed that PACA facilitates intrafibrillar mineralization by creating an amorphous calcium phosphate–rich microenvironment in the cross-linked region. Subsequently, the mineralization encapsulates the covalently cross-linked polymer and collagen fibrils within a mineralized matrix, forming an organized crystalline structure. Furthermore, PACA was used as a single-component primer in a dentin bonding model, and its impact on bonding durability was assessed through micro-tensile bond strength testing, nanoleakage analysis, and in situ zymography. These assessments demonstrate that PACA could simultaneously achieve collagen cross-linking, matrix metalloproteinase inhibition, and enhanced adhesive penetration while facilitating temporally regulated mineralization. Due to this multifunctionality, the PACA primer significantly improves micro-tensile bond strength and exhibits favorable durability after the aging experiment. This innovative approach provides a promising solution to the durability limitations of conventional adhesive systems.
{"title":"Multifunctional Primer for Dentin Bonding via Biomimetic Mineralization","authors":"S.H. Yang, Z.L. Tian, H.M. Wang, D. Sun, S.W. Qiao, Z.S. Shi, X. He, S. Zhu","doi":"10.1177/00220345251381633","DOIUrl":"https://doi.org/10.1177/00220345251381633","url":null,"abstract":"Enhancing the durability of dentin bonding remains a significant challenge in dental restoration. This study introduces an innovative approach using aldehyde-grafted polyaspartate (PACA) to achieve spatiotemporal regulation of biomimetic mineralization through collagen cross-linking. The collagen cross-linking capability of PACA was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis. Its ability to induce intrafibrillar mineralization of collagen fibrils was investigated using a rat tail collagen model through dynamic light scattering, zeta potential measurements, and transmission electron microscopy. In addition, the remineralization efficacy of PACA on demineralized dentin collagen was evaluated using scanning electron microscopy, energy dispersive X-ray spectroscopy, and atomic force microscopy. These analyses revealed that PACA facilitates intrafibrillar mineralization by creating an amorphous calcium phosphate–rich microenvironment in the cross-linked region. Subsequently, the mineralization encapsulates the covalently cross-linked polymer and collagen fibrils within a mineralized matrix, forming an organized crystalline structure. Furthermore, PACA was used as a single-component primer in a dentin bonding model, and its impact on bonding durability was assessed through micro-tensile bond strength testing, nanoleakage analysis, and in situ zymography. These assessments demonstrate that PACA could simultaneously achieve collagen cross-linking, matrix metalloproteinase inhibition, and enhanced adhesive penetration while facilitating temporally regulated mineralization. Due to this multifunctionality, the PACA primer significantly improves micro-tensile bond strength and exhibits favorable durability after the aging experiment. This innovative approach provides a promising solution to the durability limitations of conventional adhesive systems.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"63 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311095","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}
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