Comparative transcriptomic analysis of human maxillary and mandibular tooth germs

 

 reveals discrepancies in gene expression patterns

Peer-Reviewed Publication

Tsinghua University Press

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Representative images and heatmaps illustrate how human fetal tooth germs from the upper and lower jaws, although morphologically similar at the cap stage, already display distinct gene expression signatures. Maxillary tooth germs show higher expression of morphogenesis-related genes, while mandibular tooth germs are enriched for mineralization- and calcium homeostasis-related genes, highlighting early regional specialization in tooth development.

view more 

Credit: Oral Science and Homeostatic Medicine / Beijing Stomatological Hospital, Capital Medical University & Peking University School and Hospital of Stomatology

The interaction between genetics and tissue environment shapes how individual teeth form in different regions of the jaw. While most experimental studies have focused on mandibular (lower jaw) teeth, little was known about how human maxillary (upper jaw) and mandibular teeth diverge at the molecular level during early development.

 

In a new study published in Oral Science and Homeostatic Medicine, a collaborative team from Beijing Stomatological Hospital, Capital Medical University, and Peking University School and Hospital of Stomatology performed a RNA-sequencing analysis of human fetal tooth germs at the cap stage (11–12 post-conception weeks). They compared gene expression profiles between pooled maxillary and mandibular tooth germs and validated key findings with quantitative PCR and immunofluorescence staining.

 

Upper and lower tooth germs show distinct transcriptomic profiles at the cap stage

Morphologically, both upper and lower tooth germs displayed typical cap-stage features, but principal component analysis of the RNA-seq data revealed a clear separation between maxillary and mandibular samples, indicating distinct transcriptional signatures despite their similar morphology.

 

The team identified 14,267 genes that were highly expressed in both regions, enriched in pathways related to extracellular matrix organization, TGF-β, WNT, NOTCH and BMP signaling, reflecting a shared core program for epithelial–mesenchymal interactions and early odontogenesis.

 

Upper tooth germs are enriched for morphogenesis-related genes, whereas lower tooth germs are enriched for mineralization-related genes.

Beyond this common framework, 687 genes were differentially expressed between the two regions: 282 were upregulated in maxillary tooth germs and 405 in mandibular tooth germs.

 

Maxillary-enriched genes, including GATA3, SHOX2 and PAX3, were associated with embryonic organ morphogenesis, regulation of FGF and BMP signaling, and extracellular matrix remodeling. These genes have been previously implicated in craniofacial patterning, palatal development and upper jaw formation.

 

In contrast, mandibular-enriched genes such as HAND2, DLX6, NKX2-3, PHEX and DMP1 were linked to actin-based movement, calcium ion transport and homeostasis, dentinogenesis and cytokine secretion—processes that support mineralized tissue formation and mechanical function.

 

“Even though the tooth germs in the upper and lower jaws look very similar at the cap stage, their gene expression patterns are diverging,” said Ran Zhang, corresponding author of the study.

 

Protein–protein interaction network analysis highlighted several hub regulators, including IHH, HAND2, PAX3 and SP7, that connect multiple signaling pathways and may orchestrate region-specific tooth germ differentiation.

 

Validation at RNA and protein levels

To confirm the RNA-seq results, the investigators selected 18 representative genes for RT-qPCR. Most showed significant and consistent regional differences, with SHOX2, CHRDL1, GATA3, SP7 and PAX3 higher in maxillary tooth germs, and DMP1, NKX2-3, PHEX, HAND2 and DLX6 higher in mandibular tooth germs.

 

Immunofluorescence staining additionally showed that DLX6 and PHEX  were strongly expressed in mandibular tooth germs, whereas SHOX2 was predominantly expressed in the maxillary tooth germs, revealing both regional and compartment-specific expression across epithelium and mesenchyme.

 

“These region-specific regulatory programs likely contribute to the distinct eruption timing, crown morphology and functional specialization of maxillary and mandibular teeth,” said corresponding author Songlin Wang.

 

Implications and next steps

Human embryonic samples at this stage are extremely rare, so the authors acknowledge the modest sample size as a limitation but emphasize the value of obtaining direct human data rather than extrapolating solely from animal models. They suggest that functional studies in model organisms, guided by the identified hub genes and pathways, will be needed to decode how these transcriptional programs translate into jaw-specific tooth morphology.

 

The RNA-seq data from this study have been deposited in the CNGB Sequence Archive (accession CNP0008028) to facilitate reuse by the dental research community.

---

Uncovering dental caries heterogeneity in NHANES using machine learning

 A new article published in the Journal of Dental Research explores the development an integrated data-cleaning and subtype discovery pipeline using unsupervised machine learning for comprehensive analysis and visualization of data patterns in the National Health and Nutrition Examination Survey (NHANES) database.

Authored by Alena Orlenko, Cedars-Sinai Medical Center, Los Angeles, CA, USA, et al., “Uncovering Dental Caries Heterogeneity in NHANES Using Machine Learning” addresses the limitations of the NHANES, one of the largest curated repositories of nationally representative population-level health-related indicators, by establishing a data-cleaning pipeline with a novel outlier detection algorithm and unsupervised machine learning to identify phenotype subtypes within NHANES dental caries data.

“By bringing the power of machine learning to a large national data set, the authors identify key clusters of factors linked to caries in children or seniors,” said Nick Jakubovics, Editor-in-Chief of Journal of Dental Research. “The next challenge is to build on this information and find more effective methods to prevent caries in different groups of people.”

The study demonstrates a robust data-cleaning–subtype discovery pipeline that could be applied to investigate other health conditions using NHANES and similar databases for machine learning predictive modeling. Applying a comprehensive bioinformatics pipeline to NHANES data successfully identified substantial age-driven heterogeneity in dental caries, suggesting stratification is crucial for future predictive modeling. 

This integrative approach systematically addresses data quality issues and facilitates exploratory analysis to reveal data patterns associated with subtypes and variables associated with the clinical heterogeneity of caries. It uncovered novel associations between caries status, lead/pollutant exposure, specific laboratory markers and food types, as well as sleep patterns, reflecting additional disease markers in susceptible populations. This demonstrates the value of integrating data science techniques with large-scale observational data to gain deeper insights into complex, multifactorial diseases.

About the Journal of Dental Research

The IADR/AADOCR Journal of Dental Research (JDR) is a multidisciplinary journal dedicated to the dissemination of new knowledge in all sciences relevant to dentistry and the oral cavity and associated structures in health and disease. The JDR Editor-in-Chief is Nicholas Jakubovics, Newcastle University, England. Follow the JDR on Twitter at @JDentRes.

About IADR/AADOCR 

IADR is a nonprofit organization with a mission to drive dental, oral, and craniofacial research for health and well-being worldwide. IADR represents the individual scientists, clinician-scientists, dental professionals, and students based in academic, government, non-profit, and private-sector institutions who share our mission. AADOCR is the largest division of IADR. Learn more at www.iadr.org.

---

Journal

Journal of Dental Research

Article Title

Uncovering Dental Caries Heterogeneity in NHANES Using Machine Learning

Article Publication Date

9-Dec-2025

Sweet tooth: How blood sugar migration in diabetes affects cavity development

 

Researchers from The University of Osaka find that migration of blood sugar to saliva in individuals with type 2 diabetes causes an imbalance in the oral microbiome, affecting cavity development

Peer-Reviewed Publication

The University of Osaka

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Schematic overview of the study

view more 

Credit: Akito Sakanaka, Kuboniwa Laboratory, The University of Osaka

Osaka, Japan – Individuals with type 2 diabetes often have a higher incidence of tooth decay, but the underlying mechanisms remain unclear. Recent evidence indicates that hyperglycemia could lead to the overwhelming presence of sugars not only in urine but also in saliva, yet its contribution to the development, or pathogenesis, of tooth decay is still unknown.

Researchers have now been able to demonstrate that this is directly influenced by blood sugar migration to saliva, changing the bacterial populations in the mouth to promote cavity development. In a study recently published in Microbiome, researchers from The University of Osaka have revealed that blood sugar migration to saliva, induced by hyperglycemia, caused shifts in the oral microbiome that fueled cavity-associated bacteria. This migration of blood sugar was increased in individuals with dental caries, commonly known as cavities, and more dental plaque, but reduced with improved blood sugar control.

“We developed a novel method for untargeted metabolomic profiling of gland-derived saliva that preserves intact metabolite profiles before modification by the oral microbiome,” explains Masae Kuboniwa, senior author of the study. “This allowed us to understand the changes in these metabolites between the blood and saliva, and their subsequent changes after exposure to the oral microbiome.”

The team compared gland-derived saliva metabolite profiles, which provides information about an individual’s metabolic status without bacteria present, against whole saliva and plasma samples from individuals living with and without type 2 diabetes. It was found that the migration of fructose and glucose from blood to saliva was induced by hyperglycemia. Through microbial sequencing, they were then able to see the effect that this migration had on the oral microbiome.

“The increase of these metabolites in saliva fueled changes in the oral microbiome, enriching cariogenic bacteria such as Streptococcus mutans and reducing the abundance of health-associated species like Streptococcus sanguinis, shifting oral biofilm metabolism toward glycolysis and carbohydrate degradation,” says Akito Sakanaka, lead author. “This shift in the microbial population increases acid production, which erodes tooth enamel and strongly links diabetes to dental caries.”

Importantly, the team found that improved glycemic control reduces the plasma-to-saliva transfer of sugars, particularly fructose, reversing this microbiome imbalance and reducing the risk of tooth decay. In fact, a co-culture biofilm experiment with S. mutans and S. sanguinis demonstrated that the proportion of S. mutans markedly increased in a nutrient-rich medium containing fructose, indicating that the combination of glucose and fructose favors S. mutans under co-culture conditions. Together, these findings help to reveal the role of blood sugar migration to saliva in the pathogenesis of tooth decay and plaque buildup in individuals with type 2 diabetes. The findings indicate that glycemic control could be an effective strategy to reduce the risk of not only periodontal disease, an established oral comorbidity, but also tooth decay, helping to improve oral health and quality of life.

###

The article, “Diabetes alters the supragingival microbiome through plasma-to-saliva migration of glucose and fructose,” was published in Microbiome at DOI: https://doi.org/10.1186/S40168-025-02256-X

Oral bacteria from tooth infections worsens diabetes risk

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Schematic overview showing how Porphyromonas gingivalis (Pg) with intact LPS drives periapical bone loss and systemic glucose intolerance through IL-17–mediated inflammation. Pg colonization in teeth induces immune cell infiltration (CD45, CD19, Th17) and adipose tissue inflammation, worsening glucose metabolism in high-fat diet mice. These effects are reduced in mice infected with LPS-deficient Pg or lacking IL-17, highlighting IL-17’s key role in linking oral infection to metabolic dysfunction.

view more 

Credit: Vincent Blasco-Baque from INSERM/Université de Toulouse/CHU of Toulouse Image link: https://doi.org/10.1038/s41368-025-00403-6

Chronic inflammatory diseases are increasingly recognized as being tied to systemic metabolic dysfunction, overturning the old belief that local infections stay confined. Research now shows that inflammation arising in a single site like the gums or the root of a tooth can send systemic signals that disrupt glucose regulation. Oral diseases, once dismissed as dental issues, have become central to this evolving picture. Among the key culprits is Porphyromonas gingivalis (Pg), a pathogen behind gum disease and periapical lesions. With its atypical lipopolysaccharide (LPS) and strong inflammatory drive, Pg has emerged as a notable link between persistent oral inflammation and broader metabolic imbalance.

To investigate this possibility, Pr. Vincent Blasco-Baque and his research team at INSERM/Université de Toulouse conducted a comprehensive study, recently published in Volume 17 of the International Journal of Oral Science on 13 November 2025. Their goal was to determine whether Pg-driven periapical lesions could influence systemic metabolism through IL-17–mediated inflammation. Building on earlier findings linking gut bacteria and LPS to metabolic disease, the team sought to uncover whether similar mechanisms could originate from the oral cavity, specifically from endodontic infections.

The researchers first analyzed periapical tissues from 94 endodontic surgery patients and found Pg to be a predominant pathogen, particularly in severe lesions. Vincent Blasco-Baque explains “To test causation and mechanism, we developed a controlled mouse model in which the endodontic space was monocolonized with Pg. Mice were placed on a high-fat diet to simulate metabolic stress and were assigned to receive either wild-type Pg with intact LPS, a weakened LPS strain, or purified LPS alone.” An additional group lacked IL-17 to determine its role in disease progression. Across all groups, the team evaluated periapical bone loss with micro-CT, profiled immune activation, and assessed adipose inflammation, dysbiosis, and glucose metabolism.

These findings reveal a clear mechanistic link between Pg-induced periapical disease and systemic metabolic dysfunction. As Vincent Blasco-Baque shares, “Mice exposed to Pg with functional LPS showed marked periapical bone loss and a surge in Th17 cells and IL-17.” He further notes, “These effects extended systemically: in high-fat–diet mice, Pg-LPS significantly worsened glucose intolerance, accompanied by adipose dysbiosis, inflammation, and cytokines that disrupt insulin signaling.” In IL-17 knockout mice, however, this cascade largely disappeared. Pg or its LPS failed to induce substantial bone loss, metabolic impairment, or inflammatory activation. Without IL-17, Pg lost much of its capacity to drive local and systemic pathology.

This study offers several key benefits and insights. It highlights a previously underrecognized role of periapical lesions in influencing systemic metabolic health. It also establishes a robust causal model rather than solely correlational evidence. Finally, it identifies IL-17 as a potential therapeutic target, suggesting that modulating Th17 activation or blocking Pg virulence factors, such as gingipains or O-antigen LPS components, may reduce both local tissue destruction and systemic metabolic risk.

“Looking ahead, these findings open opportunities for novel interventions, including IL-17 inhibitors, gingipain blockers, microbiome-modulating approaches, and improved diagnostic biomarkers to assess systemic impact of endodontic infections.” shares Vincent Blasco-Baque.  Further research into synergistic interactions with other oral pathogens may also deepen understanding of oral-systemic disease links.

In conclusion, this study demonstrates that Pg and its LPS are potent drivers of both periapical bone destruction and systemic metabolic dysfunction, acting through an IL-17–dependent inflammatory pathway. By unveiling an oral–systemic axis connecting endodontic infection to metabolic disease, the work lays the foundation for new therapeutic strategies aimed at protecting both oral and systemic health.

***

About Vincent Blasco-Baque from INSERM/Université de Toulouse/CHU of Toulouse

Vincent Blasco-Baque is a Professeur des Universités–Hospitalier at the Université de Toulouse, where he leads the InCOMM team at the Institut des Maladies Métaboliques et Cardiovasculaires in INSERM. He holds a DMD in Dental Surgery and a PhD in Biology/Physiopathology. With more than a decade of research experience and over 80 scientific publications, his work integrates clinical studies with fundamental biological research. His studies focus on the oral and intestinal microbiota, particularly their involvement in cardiometabolic diseases, inflammation, and periodontitis. He has also coordinated large-scale multi-omics human cohorts and developed gnotobiotic mouse models to investigate causal microbe–host interactions.

Funding information

This study was supported by the Paul Calas Award from the French Society of Endodontics (SFE). The funding body had no role in the study design, data collection, analysis, interpretation, or manuscript writing. Except that, we have not received any funding, grants, or personal benefits from any organization that could affect the objectivity of this study.

---

Journal

International Journal of Oral Science

DOI

10.1038/s41368-025-00403-6 

Vitamin D levels during pregnancy and dental caries in offspring

 In this cohort study published in JAMA Network Open maternal plasma 25-hydroxyvitamin D levels throughout pregnancy were inversely associated with odds of offspring early childhood caries. These findings support the potential benefit of vitamin D supplementation before or during pregnancy in reducing the risk and severity of childhood dental caries.

---

Making quieter dental drills to reduce dental anxiety

 Dental anxiety, also known as odontophobia, prevents people from getting their regular cleanings and keeping up with necessary dental hygiene.

One aspect of the anxiety comes from the sound of the dental drill, which makes a high-pitched whining sound. As a dentist, Tomomi Yamada has witnessed discomfort and fear in her patients firsthand.

“Originally, I was doing research on dental materials, but I realized that almost no one — not even dentists — was tackling this sound problem scientifically,” Yamada said.

Yamada, an assistant professor at the University of Osaka’s graduate school of dentistry, will present her work Tuesday, Dec. 2, at 8:20 a.m. HST as part of the Sixth Joint Meeting of the Acoustical Society of America and Acoustical Society of Japan, running Dec. 1-5 in Honolulu, Hawaii.

To understand the aerodynamics of the drill, Yamada and her collaborators from the University of Osaka, Kobe University, and National Cheng Kung University used Japan’s flagship supercomputer to conduct large-scale aeroacoustics simulations. They analyzed the internal and external airflow of the dental drill, which is powered by compressed air and rotates at about 320,000 revolutions per minute.

From these simulations, they were able to visualize how air moves through and around the drill to create the noise.

“Our research showed that just making the drill quieter isn’t enough to make the sound less unpleasant,” Yamada said. “What really matters is improving its sound quality.”

The researchers also tested the psychological effects of the dental drill, which can generate high-pitched sounds reaching nearly 20 kilohertz, with children and adults. They found that younger listeners had different reactions to the drill, perceiving the sounds as louder and more unpleasant.

“This indicates that children’s fear of dental sounds is not merely psychological but also physiological in nature,” said Yamada. “Children truly hear these sounds differently, so their fear of dental treatment is a genuine sensory response, not just imagination.”

To address this, Yamada and her colleagues are working on optimizing the blade geometry and exhaust port of the drill to minimize the noise while maintaining the performance.

To get the dental industry to adopt this new technology, achieving a balance between the device’s performance and safety is key, since a quieter drill won’t necessarily get the job done.

“Moving forward, we hope to work with dental manufacturers through industry–academia partnerships, progressing toward commercialization after completing the necessary regulatory and durability testing,” Yamada said.

Root canal treatment reduces heart disease and diabetes risk

 

Caption

Root canal infections can cause bacteria to enter the blood, leading to inflammation, heart disease and diabetes risk. Successful treatment reduces these risks

Credit

King's College London

Usage Restrictions

Credit King's College London

Successful root canal treatment could reduce inflammation linked to heart disease and improve levels of blood sugar and cholesterol

Peer-Reviewed Publication

King's College London

 

image: 

Root canal infections can cause bacteria to enter the blood, leading to inflammation, heart disease and diabetes risk. Successful treatment reduces these risks

view more 

Credit: King's College London

Successful root canal treatment could reduce inflammation linked to heart disease and improve levels of blood sugar and cholesterol.

In the first of its kind research, a clinical study by King’s College London tracked changes in blood chemistry following root canal treatment for a common dental infection (apical periodontitis). The infection can cause bacteria to enter the bloodstream and increase inflammation, associated with risks to cardiac health and reduced ability to control blood sugar levels.

Despite the link between the infection and wider health impacts, the association between successful root canal treatment and the benefits to heart and metabolic health had not been investigated until now.

The team discovered that successful root canal treatment was associated with:

• Improved glucose metabolism: Blood sugar levels dropped significantly over two years after treatment, a key factor in preventing diabetes
• Better lipid profiles: Short-term improvements in blood cholesterol and fatty acid levels, which are closely linked to heart health
• Reduced inflammation: Key markers of inflammation, often linked to cardiovascular risk and other chronic conditions, decreased over time
• Oral bacteria linked to body-wide effects: Bacteria from infected teeth were associated with changes in the body’s overall metabolism

 

Root canal infections can cause bacteria to enter the blood, leading to inflammation, heart disease and diabetes risk. Successful treatment reduces these risks

The study followed the health of 65 patients from Guy's and St Thomas' NHS Foundation Trust over two years after root canal treatment. Scientists analysed molecules in the blood of patients to reveal how the body processes sugar, fat, other key substances, and responds to disease and treatment. They used a technique known as nuclear magnetic resonance (NMR) spectroscopy, used to analyse proteins in the body.

The findings suggest that monitoring blood metabolic markers, such as glucose, fats known as triglycerides, and the protein tryptophan, could help assess recovery and risk after dental treatment.

Lead Author Dr Sadia Niazi, Senior Clinical Lecturer in Endodontology, King’s College London, said: “Our findings show that root canal treatment doesn’t just improve oral health – it may also help reduce the risk of serious health conditions like diabetes and heart disease. It’s a powerful reminder that oral health is deeply connected to overall health.

“Long-standing root canal infections can allow bacteria to enter the bloodstream, trigger inflammation, and increase blood glucose and fats levels – raising the risk of serious health issues like heart disease and diabetes. It is vital that dental professionals recognise the wider impact of these root canal infections and advocate for early diagnosis and treatment.

“We also need to move towards integrated care, where dentists and general practitioners work together to monitor the risks through these blood markers and protect overall health. It’s time to move beyond the tooth and embrace a truly holistic approach to dental care.”

While more research is needed to confirm these effects in larger populations, the study opens exciting new doors for understanding how oral care can support general health and wellbeing.

This study is published in Journal of Translational Medicine.

Notes to Editors

Funding

This study was funded by Royal College of Surgeons (RCS) England.

Images – credit King’s College London

---

Journal

Journal of Translational Medicine