New study reveals key role of inflammasome in male-biased periodontitis

A study out of the University of North Carolina at Chapel Hill has unveiled new insights into the inflammatory processes behind periodontitis, a common and debilitating gum disease. Research conducted by UNC Adams School of Dentistry’s Julie Marchesan, DDS, PhD, and UNC School of Medicine’s Jenny Y. Ting, PhD, found that a part of the immune system called the inflammasome plays a key role in disease development, and that blocking this system prevents bone resorption only in males.

The study, published in the journal Proceedings of the National Academy of Sciences, suggests developing treatments specifically for male patients can have benefits and prompted an exploration of different biological mechanisms responsible for bone loss in females.

Periodontitis, inflammation-driven bone loss around the teeth, affects millions of people worldwide. While the disease is common across genders, it disproportionately impacts men, with males experiencing more severe symptoms.

“Our paradigm-shifting work not only pinpoints the inflammasome as a causal driver of male-biased periodontitis but also demonstrates a clear path for the development of sex-stratified therapeutics in periodontics,” Marchesan said. “Prior to this work, the inflammasome was believed to have the same role in the development of inflammatory conditions in both females and males. Our findings will foster the development of therapies that target the inflammasome and can specifically benefit male patients, while also paving the way for the discovery of biological mechanisms responsible for periodontitis in females.”

The study analyzed more than 6,200 human samples across three independent studies. Its findings showed that males exhibit significantly higher levels of interleukin-1 beta (IL-1β) in the gingival crevicular fluid during both healthy and periodontitis-affected states. This finding suggests that males may be more susceptible to inflammation-driven bone loss due to heightened IL-1β activity.

To further investigate this, the research team used mouse models and found male mice displayed greater IL-1β secretion than females. In addition, male mice with inflammasome gene deletions showed reduced bone loss. Applying a pharmacologic caspase-1/4 inhibitor to block inflammasome activity led to a significant reduction in inflammatory cell infiltration and a decrease in osteoclastogenesis signaling, which contributes to bone resorption. This intervention was effective in male mice but did not impact female mice, suggesting that the inflammasome’s role in periodontitis is gender-specific.

Researchers also tested male and female mice with their testes and ovaries removed, and found that male mice lost their response to caspase-1/4 inhibition. The female mice showed no change in their lack of response, further supporting the idea that the male reproductive system plays a crucial role in inflammasome-driven inflammation.

The study highlights the need for sex-specific research to fully understand the mechanisms behind inflammatory diseases. Given the prominent role of the inflammasome in driving male-biased periodontitis, further investigation into inflammasome-targeted treatments may offer a new avenue for improved patient care.

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.250709212 

Decision on dental amalgam secures an equity-focused, patient-centred approach

 

 A landmark decision was reached at the Sixth Conference of the Parties (COP6) to the Minamata Convention on Mercury, where Parties agreed to set 2034 as the global phase-out date after which the manufacture, import, or export of dental amalgam will no longer be permitted. This milestone marks a major win for oral and public health and underscores the power of unified, science-based advocacy led by FDI World Dental Federation (FDI) and the International Association for Dental, Oral, and Craniofacial Research (IADR).

The final decision reflects a balanced and equity-focused approach to phasing down dental amalgam use worldwide. Crucially, it includes a key exemption that supports the joint advocacy by FDI and IADR, which ensures that even after phase-out of dental amalgam it can be used “when its use is considered necessary by the dental practitioner based on the needs of the patient.” This provision ensures that patient care remains at the center of decision-making, safeguarding access to essential restorative treatments where alternatives are not yet available or viable.

FDI and IADR, with the support of the International Dental Manufacturers Association (IDM) and the American Dental Association (ADA), worked tirelessly to secure a balanced outcome by actively engaging in and influencing discussions throughout the negotiations. Coordinated advocacy efforts emphasized that while accelerating the phase down and eventually phasing out dental amalgam is essential, it must be achieved through an evidence-based, patient-centered, and equitable transition that is fair to all countries and considers their specific challenges and capacities.

“As we move toward the eventual phase-out of dental amalgam, it is essential that the needs of our members, and the patients they serve, remain at the heart of every decision,” said Mr Enzo Bondioni, Executive Director of FDI. “This outcome provides much-needed time and clarity for our members to plan, prepare, and implement the necessary national policies. It reinforces FDI’s commitment to supporting the global dental community in maintaining continuity of care and advancing oral health equity during this important transition”.

Over four days of intense deliberation, both organizations delivered individual and joint statements reinforcing the continued relevance of dental amalgam in restorative dentistry, while emphasizing the importance of prevention. They called for research into affordable, effective, and sustainable alternative materials and emphasized that waste management should be compulsory to reinforce the Convention’s broader objective of reducing environmental mercury exposure. These concerted efforts helped ensure that the final phase-out timeline was extended beyond 2030, the date originally proposed to 2034.

“Science and evidence must remain at the heart of every global health policy decision,” said Dr Christopher Fox, Chief Executive Officer of IADR. “This outcome reflects the progress we’ve made by investing in research into mercury-free alternatives, as called for in the text of the Minamata Convention, from both the public and private sectors. “IADR remains committed to supporting continued innovation and research that will further the rapid improvement of affordable, effective, and sustainable restorative materials, so no one is left behind in this transition”.

The decision gives Parties nine years to adapt their national strategies and healthcare systems to this new framework. This aligns closely with FDI and IADR’s long-standing position advocating for a coordinated and equity-focused phase-down that allows all countries, especially low- and middle-income nations, to strengthen capacity, build technical expertise, and ensure continuity of patient care during the transition.

By recognizing the diverse realities of healthcare delivery worldwide, the 2034 phase-out date and practitioner-based exemption together provide flexibility that avoids widening existing oral health inequalities. The Minamata Convention on Mercury, which entered into force in August 2017, now counts 153 Parties as of September 2025. The Seventh Conference of the Parties (COP7) will take place in June 2027, coinciding with the tenth anniversary of the Convention.

About FDI World Dental Federation (FDI)

FDI World Dental Federation is the leading global voice of the dental profession and envisions a world with optimal oral health. It serves as the principal representative body for over 1 million dentists worldwide. Its membership includes some 200 national dental associations and specialist groups in over 130 countries. www.fdiworlddental.org/

About International Association for Dental, Oral, and Craniofacial Research (IADR)

The International Association for Dental, Oral, and Craniofacial Research (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. Learn more at www.iadr.org.

Non-prescription pain meds work equally well for men and women after tooth extraction

 

Over-the-counter pain medications work as well or better than opioids after wisdom tooth extraction for both men and women, according to a Rutgers Health-led follow-up to a landmark paper on comparative pain relief.

That first paper on the collective experience of more than 1,800 trial patients found that the combination of ibuprofen and acetaminophen provided better pain relief than hydrocodone with acetaminophen for the first two days after surgery and greater satisfaction over the post-operative period. The new subgroup analysis, published in JAMA Network Open, demonstrated that the results held for both male and female patients.

"We wanted to determine whether the pain medication’s effects were consistent in males and females separately," said Janine Fredericks Younger, an associate professor at Rutgers School of Dental Medicine and lead author of the analysis. "And what we found is that in both subgroups (males and females), the non-opioid was superior for that first day and night, and then no worse than the opioid for the rest of the post-op period."

The trial that produced both papers, funded by an $11 million grant from the National Institutes of Health, compared patients who received 400 milligrams of ibuprofen (Advil, Motrin) combined with 500 milligrams of acetaminophen (Tylenol) against those who got 5 milligrams of hydrocodone with acetaminophen. 

The gender-specific analysis was particularly important because women consistently report higher pain levels after surgery, raising questions about whether pain medications work differently for each sex. 

"There's obviously different biological mechanisms, different hormones involved," said Cecile Feldman, dean of Rutgers School of Dental Medicine and senior author of both studies. "But results confirm that the analgesic effect for both groups is the same."

The researchers deliberately enrolled equal numbers of men and women from the start, allowing them to conduct robust subgroup analyses. Patients across five universities tracked their pain twice daily for nine days using electronic diaries, rating not just pain but also sleep quality, ability to perform daily activities and overall satisfaction.

On every measure, the over-the-counter combination matched or beat the opioid. Patients taking the non-opioid medications reported better sleep quality and less interference with daily activities. Those who received opioids were twice as likely to call back requesting additional pain medication.

"The results actually came in even stronger than we thought they would," Feldman said. "We expected to find the non-opioid to be non-inferior, so that at least it was no worse than opioids. We were surprised to see that it was actually superior."

Dental procedures are a common entry point for opioid exposure. Dentists wrote more than 8.9 million opioid prescriptions in 2022, ranking among the nation's leading prescribers of the drugs.

"There are studies out there to show that when young people get introduced to opioids, as many have via wisdom tooth extraction, there's an increased likelihood that they'll eventually use them again, and then it can lead to addiction," said Fredericks Younger, noting that opioid overdoses kill more than 80,000 Americans annually.

The research focused on the extraction of impacted wisdom teeth, which requires cutting into gums and sometimes removing bone, making it one of the most painful dental procedures. The Food and Drug Administration uses this as a standard model for testing pain medications because it reliably produces moderate to severe pain for about 48 hours.

Feldman said the results, showing the superiority of the over-the-counter medication to opioids, likely apply to other dental procedures but cannot be automatically generalized to surgeries in other parts of the body. She would like to see similar studies conducted for a range of procedures, particularly those for orthopedic injuries, which frequently result in opioid prescriptions for high school and college athletes.

Despite mounting evidence, many dentists continue writing "just in case" opioid prescriptions for patients who are told to start with over-the-counter medications. The next phase of research will examine why these prescribing patterns persist.

"How can we now, with the evidence and the knowledge that we have, eliminate these prescriptions from being written?" Fredericks Younger said.

The findings align with American Dental Association recommendations to avoid opioids as first-line pain treatment. Feldman said the study's results leave little room for doubt.

"We feel pretty confident in saying that opioids should not be prescribed routinely for dental procedures," she said. "Our non-opioid combination really should be the analgesic choice."

---

Journal

JAMA Network Open

DOI

10.1001/jamanetworkopen.2025.42467 

Scientists find cells that know when, where, and how to grow teeth

 Tooth development is a dynamic process that involves the stages of the bud, the cap, and the bell, followed by root development and subsequent tooth formation. Processes such as the bud-to-cap transition are mediated by epithelial-mesenchymal interactions. In addition, the position of a cell in a developing embryo determines its fate due to the relative differences in concentration of signaling molecules and growth factors.

Scientists have long known that a single tooth develops as a small bud of outer “epithelial” cells into the deeper “mesenchymal” cells. It then curves to form a cap shape and then folds in further to form the bell shape of a mature tooth, with surrounding bone and gums. Dr. Han-Sung Jung and his team at the Yonsei University College of Dentistry, Korea, extended these findings by examining how the position of young epithelial and mesenchymal dental cells would influence what they grow into and have published their findings in International Journal of Oral Science.

Lead author Dr. Jung said that his team “performed this study to identify how positional identity along the lingual-buccal axis determines distinct developmental fates of dental mesenchyme. This research has the potential to significantly impact our understanding of tooth development,” he says.

The investigators separated the mesenchymal cells on the lingual and buccal sides at both cap and bell stages of a developing mouse embryo and -compared their gene expression profiles through RNA-seq followed by Gene Ontology enrichment analysis to understand the differences with position and time. They then transplanted the cap-stage lingual and buccal cells separately under the kidney capsule of immunocompromised mice to see what each grew into. Analysis showed that cells on the lingual side were mainly geared toward making the tooth itself and shaping its structure, while cells on the buccal side were more focused on stem cell activity, forming surrounding tissues, and supporting tooth growth and repair. Not surprisingly, only the lingual cells in the mouse kidney grew into tooth enamel.

The researchers also reported haphazardly mixing up cap-stage, tagged buccal and lingual cells of genetically engineered mice. “We were curious to know if they could find their original place and reorganize when the fluorescently labled lingual and buccal mesenchymal cells were mixed randomly, which they not only did, but the lingual cells grew into dentin to form the tooth as before. This phenomenon is called cellular self-organization,” says first author Eun-Jung Kim.

Furthermore, they have extensively studied the signalling molecules in each group and found that WNT signalling and R-spondins (Rspo1/2/4) are enriched in lingual cells, along with high proliferation, low cell death, and higher migration rate, aiding tooth formation. On the other hand, buccal cells show increased expression of  BMP inhibitors, lower proliferation, higher apoptosis, and slower migration, favoring bone and surrounding tissue formation.

In conclusion, the authors proposed a model of dental cell positioning based on the lingual-buccal axis for tooth and surrounding tissue formation. The characteristics of dental mesenchymal cells were found to vary along this axis, and the fate of the tooth and surrounding tissue formation is determined by mesenchymal cells via WNT/BMP signaling. Deeper knowledge of the molecular nuances of tooth development will inspire further research in tissue engineering and regenerative medicine, which may ultimately lead to advancements in stem cell-based tooth regeneration and more effective therapeutic applications for dental restoration and repair.

 

***  
 

Reference
DOI: https://doi.org/10.1038/s41368-025-00391-7

---

Journal

Gum disease and cavities linked to increased stroke risk

 

Highlights:

• A new study finds that having both gum disease and cavities is linked to an 86% increased risk of stroke compared to having a healthy mouth.
• Poor oral health was tied to a 36% higher risk of heart attacks and other cardiovascular events.
• People with regular dental visits were 81% less likely to have both gum disease and cavities.
• Researchers say improving oral health could be an important — and often overlooked — way to help reduce stroke risk.

MINNEAPOLIS – People with both cavities and gum disease may face a higher risk of ischemic stroke, according to a study published on October 22, 2025, in Neurology® Open Access, an official journal of the American Academy of Neurology. The study does not prove that poor oral health causes strokes; it only shows an association.

Ischemic strokes are the most common type of stroke and occur when a clot or blockage reduces blood flow to the brain, depriving it of oxygen and nutrients.

Cavities are holes in the tooth enamel caused by sugary or starchy foods or factors such as poor oral hygiene or genetics. Gum disease, usually caused by poor oral hygiene, is an inflammation or infection of the gums and jawbone. It can lead to tooth loss.

“We found that people with both cavities and gum disease had almost twice the risk of stroke when compared to people with good oral health, even after controlling for cardiovascular risk factors,” said study author Souvik Sen, MD, MS, MPH, of the University of South Carolina in Columbia. “These findings suggest that improving oral health may be an important part of stroke prevention efforts.”

Researchers analyzed data from 5,986 adults with an average age of 63 who had no prior history of stroke at the start of the study. All participants completed dental exams that assessed whether participants had gum disease, cavities or both. Participants were then placed in three groups: having a healthy mouth, gum disease only or gum disease with cavities.

Researchers followed them for two decades, using phone visits and medical records to determine which people had a stroke.

Of 1,640 people with healthy mouths, 4% had a stroke, of 3,151 people with gum disease only, 7% had a stroke and of 1,195 people with gum disease and cavities, 10% had a stroke.

After adjusting for factors such as age, body mass index and smoking status, researchers found when compared to people with healthy mouths, those with both gum disease and cavities had an 86% higher risk of stroke. Those with gum disease alone had a 44% increased risk.

The study also looked more broadly and found that people with both gum disease and cavities had a 36% higher risk of experiencing a major cardiovascular event, such as a heart attack, fatal heart disease or stroke when compared to people with healthy mouths.

Participants who reported visiting the dentist regularly had 81% lower odds of having both gum disease and cavities and 29% lower odds of having gum disease alone.

“This study reinforces the idea that taking care of your teeth and gums isn’t just about your smile; it could help protect your brain,” said Sen. “People with signs of gum disease or cavities should seek treatment not just to preserve their teeth, but potentially to reduce stroke risk.”

A limitation of the study is that participants’ oral health was assessed only once at the start of the study, so changes in dental health over time weren’t captured. It’s also possible that other unmeasured health factors contributed to the findings.

Gum disease associated with changes in the brain

 Adults with gum disease may be more likely to have signs of damage to the brain’s white matter, called white matter hyperintensities, than people without gum disease, according to a new study published on October 22, 2025, in Neurology® Open Access, an official journal of the American Academy of Neurology.

White matter refers to nerve fibers that help different parts of the brain communicate. Damage to this tissue can affect memory, thinking, balance and coordination and has been linked to higher stroke risk.

White matter hyperintensities are bright spots that appear on brain scans that are thought to reflect damaged white matter tissue. While the study found an association, it does not prove that gum disease causes white matter damage.

“This study shows a link between gum disease and white matter hyperintensities suggesting oral health may play a role in brain health that we are only beginning to understand,” said study author Souvik Sen, MD, MS, MPH, of the University of South Carolina in Columbia. “While more research is needed to understand this relationship, these findings add to growing evidence that keeping your mouth healthy may support a healthier brain.”

The study included 1,143 adults with an average age of 77. Each person had a dental exam to check for gum disease. Of participants, 800 had gum disease and 343 did not.

Participants had brain scans to look for signs of cerebral small vessel disease, which is damage in the brain’s small blood vessels that can appear as white matter hyperintensities, cerebral microbleeds or lacunar infarcts. These brain changes become more common with age and are associated with increased risk of stroke, memory problems and mobility issues.

People with gum disease had more white matter hyperintensities, with an average volume of 2.83% of total brain volume compared to 2.52% for people without gum disease.

Researchers divided people into four groups based on white matter hyperintensity volume. Those in the highest group had a volume of more than 21.36 centimeters cubed (cm³) while those in the lowest group had a volume of less than 6.41 cm³.

Of people with gum disease, 28% were in the highest group compared to 19% of people without gum disease.

After adjusting for factors such as age, sex, race, high blood pressure, diabetes and smoking, people with gum disease had 56% higher odds of falling into the highest group of white matter hyperintensities than people without gum disease.

However, no links were found between gum disease and two other brain changes tied to small vessel disease, cerebral microbleeds and lacunar infarcts.

“Gum disease is preventable and treatable,” said Sen. “If future studies confirm this link, it could offer a new avenue for reducing cerebral small vessel disease by targeting oral inflammation. For now, it underscores how dental care may support long-term brain health.”A limitation of the study is that brain imaging and dental assessments were conducted only once, making it difficult to assess changes over time.

Researchers explore drill-free treatments for cavities in older adults

 A trip to the dentist isn’t something people usually look forward to.

“Because of all the drilling and injections, it’s not fun,” acknowledged Suchitra Nelson, an associate dean and professor at the Case Western Reserve University School of Dental Medicine.  

While discomfort can’t be entirely avoided in all dental procedures, Nelson is leading a new study to advance previous research that found two less-invasive options to treat and prevent cavities were equally effective.

The study focuses on older adults living in subsidized housing with limited access to dental care because of such barriers as dental insurance, transportation and their overall general health—especially mobility.

As with the previous study, the patients will be treated for cavities with two methods that don’t require a dental drill or anesthesia: Silver Diamine Fluoride (SDF) and Atraumatic Restorative Treatment (ART).

SDF, a liquid medication applied to cavities to stop them from progressing, is a quick and painless treatment that kills bacteria and strengthens the tooth’s surface, Nelson said. And ART involves removing decayed tissue with hand instruments and then applying a dental restorative material.

“Long-term evidence for these treatments is lacking,” Nelson said. “This long-term follow-up study can inform the best treatments for patients and providers to prevent and treat tooth decay.”

The study is being supported with a five-year, $5 million grant from the nonprofit Patient-Centered Outcomes Research Institute (PCORI).

Among older adults nationally, nearly 96% have had a cavity, and 33% of non-Hispanic Black, Hispanic and low-income older adults have teeth with decay that has gone untreated because of limited access to affordable dental care, according to according to the Centers for Disease Control’s National Center for Health Statistics.

Untreated tooth decay leads to painful toothaches, infection and tooth loss. But the related health concerns are much broader: Major dental issues can make heart and lung disease and diabetes worse.

In Nelson’s previous PCORI-funded study, 568 participants received either SDF or ART to prevent cavities. Participants received dental exams, treatments for cavities and completed surveys. The research found that the two treatments were equally effective in preventing cavities.

“We also found that dental hygienists can successfully deliver dental care at the housing facilities where older adults live,” Nelson said.

The new study will follow up with 480 of the patients living in 33 subsidized housing facilities in Northeast Ohio. The follow-up participants will be tracked for three visits over a year and receive the same treatments (SDF or ART) for any new cavities.

While the subject of the studies is older adults, Nelson said less invasive treatments could be used for patients of any age.

“Our stakeholder partners from local, state and national organizations have enthusiastically indicated that they would use the results of our work to make changes that improve access and clinical care, improve Medicaid policies for reimbursement and make the study’s results widely available,” she said.