Journal of Dental Research最新文献

{"title":"TMD Diagnosis Using a Masked Self-Supervised Tabular Transformer.","authors":"Y-H Lee,J H Lee,Q-S Auh,S Lee,D Nixdorf,A Chaurasia","doi":"10.1177/00220345251376974","DOIUrl":"https://doi.org/10.1177/00220345251376974","url":null,"abstract":"Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Diagnosis remains challenging due to overlapping symptoms, multifactorial etiology, and variability across clinical settings. To address these limitations, we developed the Gated Attention Tabular Transformer (GATT), a novel deep-learning model that uses masked self-supervised learning and gated attention mechanisms, to classify TMD subgroups based on the diagnostic criteria for TMD (DC/TMD). A total of 4,644 structured clinical records from a university-based registry were analyzed, comprising 3,524 female and 1,120 male patients (mean age 36.9 ± 14.7 y), across 12 core TMD subgroups. GATT achieved robust diagnostic performance with area under the receiver-operating characteristic curve values ranging from 0.815 to 1.000, sensitivity from 0.652 to 1.000, and specificity from 0.773 to 1.000. The model significantly outperformed conventional machine-learning methods including logistic regression, random forest, support vector machine, and XGBoost as well as advanced tabular deep-learning models such as TabNet, TabTransformer, AutoGluon Tabular Predictor, and FT-Transformer. Shapley additive explanations (SHAP) analysis revealed \"pain-free opening\" (SHAP = 6.78, P < 0.001) and \"current TMJ noise\" (SHAP = 2.87, P = 0.003) as key features of mechanical TMJ disorders. Co-occurrence network analysis uncovered side-specific clustering and potential time-lagged progression between bilateral TMJs. These findings demonstrate the feasibility of using deep learning to classify heterogeneous TMD subgroups using only structured clinical data, without the need for imaging. The GATT model offers an accurate, explainable, and scalable tool to support clinician-assisted diagnosis and reduce variability in TMD management in real-world practice. These results support the integration of AI-driven tools such as GATT into clinical workflows for standardized, efficient, and patient-specific TMD diagnosis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"3 1","pages":"220345251376974"},"PeriodicalIF":7.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351708","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":"Sulfur Species in Zinc-Rich Condylar Zones of a Rat Temporomandibular Joint.","authors":"B H Lee,Z Yang,Y Wang,J Levy,N Tamura,S Webb,S Bone,S P Ho","doi":"10.1177/00220345251361124","DOIUrl":"https://doi.org/10.1177/00220345251361124","url":null,"abstract":"We performed synchrotron-based micro-X-ray absorption near-edge spectroscopy (µ-XANES) coupled with micro-X-ray fluorescence (µ-XRF) for the identification of elements that included biometal zinc (Zn) and nonmetal sulfur (S) (and its species) in the condylar zones of a rat temporomandibular joint (TMJ). Zone-specific spatial localization of biometal Zn and nonmetal S from a materials viewpoint when correlated with hypoxia inducible factor-1α (HIF-1α) (a surrogate for tissue oxygenation) can provide insights into Zn-specific redox pathways at the vulnerable subchondral interface. Histologic localization of Zn, HIF-1α, and sulfur-rich proteoglycans (PGs) were mapped using an optical microscope. The µ-XRF maps coupled with site-specific micro-X-ray diffraction (µ-XRD) patterns were used to underline Zn-incorporated biological apatite in the subchondral bone and the bone of a rat TMJ condyle. Results demonstrated an association between Zn, PG, and HIF-1α histologic maps with µ-XRF, µ-XANES, and µ-XRD data and provided insights into plausible biological S species in Zn-enriched zones of a rat TMJ condyle. Spatially localized Zn and S underscore their roles in cell and tissue functions in a zone-specific manner. Elemental Zn with organic and inorganic S species at the cartilage-bone interface and the biomineral phase of Zn-enriched biological apatite from subchondral bone to condylar bone were ascertained using µ-XRF-XANES and µ-XRF-XRD. The coupled µ-XRF-XANES in situ complemented with µ-XRF-XRD in situ and immunohistochemistry provided valuable biological insights into zone-specific biological pathways in rat TMJ condyles. Based on these data, we present a workflow to reliably map and correlate S species within Zn-enriched regions of cartilage, bone, and their interface. We suggest the use of this correlative and complementary microspectroscopic spatial information for zone-specific localization of biometal Zn and nonmetal S to gain insights into plausible microanatomy-specific oxidative stress in the TMJ.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"201 1","pages":"220345251361124"},"PeriodicalIF":7.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351772","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":"Uncovering the Genetic Architecture of NSCPO in Chinese via Subtype GWAS.","authors":"Y You,Y Li,S Zhang,M Yao,J Sun,H Liu,B Shi,Z Jia","doi":"10.1177/00220345251378124","DOIUrl":"https://doi.org/10.1177/00220345251378124","url":null,"abstract":"Nonsyndromic cleft palate only (NSCPO) significantly impairs swallowing and speech, reducing quality of life. While surgical interventions offer some improvement, full recovery remains challenging, underscoring the need for a deeper understanding of its etiology. This study aimed to investigate the genetic architecture of nonsyndromic cleft palate only (NSCPO) in the Han Chinese population, focusing on identifying novel susceptibility loci by leveraging data from previous genome-wide association studies and functional genomic datasets from the ENCODE project. We identified significant associations between NSCPO subtypes (incomplete cleft palate and hard and soft cleft palate) and variants such as rs660975 in IRF6, rs3758244 in CDC37L1, and rs4880224 in BNIP3. Functional validation studies, including chromatin conformation capture and dual-luciferase assays, demonstrated that these single-nucleotide polymorphisms influence enhancer activity, thereby affecting gene expression. In addition, subtype-specific analyses revealed novel associations that may be obscured in mixed phenotypic cohorts. The findings highlight the importance of investigating genetic contributions at the subtype level to elucidate the complex etiology of cleft palate and demonstrate that the associated variants have functional effects in vitro, suggesting their roles in the pathogenesis of NSCPO.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"100 1","pages":"220345251378124"},"PeriodicalIF":7.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338828","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":"Decoding Spatiotemporal Microenvironmental Changes in Oral Carcinogenesis.","authors":"D Yang,Z Wang,Q Shang,P Yuan,S Pan,W Li,J Cai,J Yang,D Zhang,Q Chen,H Dan,H Xu","doi":"10.1177/00220345251378087","DOIUrl":"https://doi.org/10.1177/00220345251378087","url":null,"abstract":"Oral carcinogenesis is a multistage process involving epithelial hyperplasia, dysplasia, and carcinoma. Understanding the dynamic changes within the microenvironment during this process is critical for preventing disease progression. In this study, we conducted a multi-omics spatiotemporal analysis to unravel microenvironment remodeling in the carcinogenesis of oral mucosa. Our analysis identified a subset of oral epithelial progenitor cells (OEPCs) with high IGFBP2 expression. These IGFBP2high OEPCs exhibited enhanced proliferative capacity and diminished differentiation potential, implicating their pivotal role in carcinogenesis. Additionally, we observed increasing infiltration of regulatory B cells (Bregs) during the precancerous stages. The interaction between Bregs and IGFBP2high OEPCs was amplified via the TGF-β signaling pathway. Spatial transcriptomics confirmed the close proximity and interaction of these 2 cell types. Experiments revealed a progressive increase in IGFBP2high OEPCs and Bregs during the precancerous stages. However, as cancer advanced, the infiltration of Bregs stagnated and even declined. This finding suggests that while tumor initiation and progression represent a continuous process, the regulatory mechanisms involved may not remain entirely the same across these stages. Consequently, focusing exclusively on the cancerous stage risks overlooking abnormalities that emerge during the precancerous phase. In conclusion, this study integrates multi-omics spatiotemporal data to uncover the evolution of the microenvironment during the carcinogenesis of oral mucosa. Specifically, Bregs were observed to gradually accumulate and spatially associate with IGFBP2high OEPCs via the TGF-β signaling pathway, correlating with a disrupted balance between proliferation and differentiation, which may contribute to triggering malignancy.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"129 1","pages":"220345251378087"},"PeriodicalIF":7.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338824","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":"Beyond the Surface: Mechanical and Porosity Gradients in Eroded Enamel.","authors":"H L Ooi,D Bartlett,A Almansour,A LeBlanc,D White,A Morrell,O Addison","doi":"10.1177/00220345251385464","DOIUrl":"https://doi.org/10.1177/00220345251385464","url":null,"abstract":"Enamel erosion alters the structural integrity of the tooth surface, which can be measured using indentation techniques. However, traditional single-load indentation methods assume homogeneity within the eroded enamel, overlooking potential stratification within the subsurface lesion. This study investigates the presence of mechanical and porosity gradients within the enamel following simulated dietary acid exposure and examines how lesion depth and structure change with continued erosion. We applied varying-load micro-indentation to human enamel subjected to citric acid challenge, revealing a distinct stratification of mechanical properties. A soft superficial layer (~1- to 2-µm thick) exhibited significantly reduced hardness and was easily removed by ultrasonication, indicating its fragility. Beneath this layer, mechanical properties stabilized despite prolonged acid exposure (~3 min), suggesting a saturation point in lesion development. Profilometric analysis confirmed that although material loss increased with erosion time, the depth of the altered subsurface zone remained constant. To explore the porosity distribution, we used a novel gold nanoparticle labeling technique coupled with synchrotron-based X-ray fluorescence imaging. Nanoparticles (~20 nm) penetrated to depths of 15 to 20 µm, aligning closely with mechanical gradients inferred from indentation measurements. These findings indicate that subsurface enamel exhibits not only mechanical stratification but also corresponding variations in porosity. Our results demonstrate the limitations of single-load indentation in characterizing erosion-affected enamel and highlight the utility of multiload approaches in detecting structural heterogeneity. The correlation between mechanical softening and increased porosity suggests that the enamel subsurfaces are differentially affected. These findings raise important implications for therapeutic intervention: should remineralization strategies shift from bulk mineral delivery to layer-specific, functionally informed repair?","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"2 1","pages":"220345251385464"},"PeriodicalIF":7.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338807","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":"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}

{"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}

{"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}

{"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}

{"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}