Unlocking faster orthodontic treatments: the role of atf6 in bone remodeling

 

Peer-Reviewed Publication

West China Hospital of Sichuan University

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

This diagram illustrates the role of macrophage ATF6 in orthodontic tooth movement. When corticotomy is applied, monocytes are recruited to the bone, where they differentiate into pro-inflammatory macrophages. These macrophages activate ATF6, which then enhances the transcription of TNFα by binding to its promoter. This process accelerates osteoclast activity, promoting bone resorption and speeding up tooth movement. The diagram highlights key molecular interactions, including the activation of ATF6 and its interaction with the TNFα promoter.

view more 

Credit: International Journal of Oral Science

Orthodontic treatments often take years, but a breakthrough discovery could drastically shorten this period. Researchers have uncovered that ATF6, a protein activated in macrophages during corticotomy, accelerates tooth movement by promoting inflammation and boosting the production of TNFα, a key factor in bone remodeling. This finding paves the way for faster, more efficient orthodontic procedures, minimizing both treatment time and patient discomfort. The study highlights the potential for non-invasive therapies that could reshape the future of orthodontic care.

Corticotomy, a surgical procedure aimed at accelerating tooth movement, induces bone remodeling through a phenomenon known as the regional acceleratory phenomenon (RAP). While this technique is effective, the molecular mechanisms behind RAP are not yet fully understood. Macrophages, crucial players in immune responses and bone remodeling, have been identified as key participants in this process. However, the precise role of molecules like ATF6, which controls stress responses in cells, remains elusive. Based on these knowledge gaps, there’s a clear need for more focused research to understand how ATF6 influences bone remodeling in corticotomy.

This research (DOI: 10.1038/s41368-025-00359-7), led by Zhichun Jin, Hao Xu, Weiye Zhao, and their team from the Department of Orthodontics at Nanjing Medical University, was published on April 1, 2025, in the International Journal of Oral Science. The study highlights the crucial role of macrophage ATF6 in accelerating orthodontic tooth movement during corticotomy. The researchers discovered that activation of ATF6 in macrophages increases the production of TNFα, a cytokine key to bone resorption. This process accelerates bone remodeling, facilitating faster tooth movement. The study suggests that ATF6 could be a potential target for future non-invasive orthodontic treatments, providing a path for more efficient orthodontic care.

The study used advanced murine models to explore the relationship between macrophage ATF6 and orthodontic tooth movement. Researchers found that corticotomy-induced activation of ATF6 in macrophages triggered a pro-inflammatory response, significantly accelerating the movement of teeth. The presence of pro-inflammatory macrophages in periodontal tissue indicated enhanced bone remodeling. When ATF6 was genetically knocked out in macrophages, the acceleration of tooth movement was reduced. Conversely, overexpressing ATF6 intensified the process. Further analysis revealed that ATF6 directly interacts with the Tnfα promoter, enhancing the transcription of this crucial cytokine. This discovery opens new avenues for targeted treatments that could improve the speed and effectiveness of orthodontic procedures.

"Macrophage ATF6 has proven to be a key regulator in orthodontic bone remodeling," said Prof. Bin Yan, a leading researcher involved in the study. "This protein not only accelerates tooth movement by influencing inflammation but also provides us with a new therapeutic target that could revolutionize orthodontic treatments, making them quicker and less invasive."

This research holds significant promise for the future of orthodontics. By targeting the ATF6-TNFα pathway, new therapies could be developed to accelerate tooth movement without the need for surgery. Such advancements could make orthodontic procedures faster, less painful, and more accessible. Beyond orthodontics, this study could have broader applications in bone healing and treatment for diseases involving bone loss. With further research, these findings could lead to the development of non-invasive, more effective treatments for bone-related conditions, ultimately transforming patient care across multiple fields.

###

References

DOI

10.1038/s41368-025-00359-7

Original Source URL

https://doi.org/10.1038/s41368-025-00359-7

Poor oral health linked with body pain and migraines in women

The study identified specific oral microbes correlated with certain pain conditions

Peer-Reviewed Publication

University of Sydney

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

New research from the University of Sydney has revealed poor oral health is significantly associated with higher instances of migraines, abdominal and body pain in women. 

Published in Frontiers in Pain Research, the world-first study identified specific oral microbes correlated with certain pain conditions, suggesting a potential relationship between the oral microbiome and the nervous system.   

The findings highlight the importance of good oral health to potentially mitigate pain and improve overall wellbeing, prompting further exploration into the role of oral microbiota in chronic unexplained pain conditions. This includes fibromyalgia, a condition experienced by 67 percent of the study participants. 

“This is the first study to investigate oral health, oral microbiota and pain commonly experienced in women with fibromyalgia, with our study showing a clear and significant association between poor oral health and pain," said lead investigator Associate Professor Joanna Harnett from the Faculty of Medicine and Health. 

“Our findings are particularly important to fibromyalgia which, despite being a common rheumatological condition, is often underrecognised,” said first author and PhD candidate in the Faculty of Medicine and HealthSharon Erdrich.  

“Fibromyalgia is a chronic condition characterised by widespread musculoskeletal pain, and headaches including headaches, as well as fatigue, sleep disturbances, and cognitive problems.” 

How the research worked  

The research examined associations between self-reported oral health, the oral microbiome, and various pain presentations in a group of New Zealand women with and without fibromyalgia.   

Oral health was assessed using the WHO oral health questionnaire and evaluated against body pain, headaches, migraines, and abdominal pain using validated instruments, including the Short-form 36 (which measures quality of life), the International Headache Society headache survey and the functional bowel disorder severity index. Strong associations were evident between oral health scores and pain and each of these were associated with specific microbes found in the mouth, which were assessed using advanced genomic technology.   

Participants with the poorest oral health were more likely to suffer from higher pain scores: 60 percent were more likely to experience moderate to severe body pain, and 49 percent were more likely to experience migraine headaches. Lower oral health was a statistically significant predictor of frequent and chronic migraine. 

Four oral microbial species from the Dialister, Fusobacterium, Parvimonas and Solobacterium genera were significantly associated with pain after age, BMI and added dietary sugars were considered.   

A weak but significant inverse correlation with diet quality and oral health was also found, though the researchers note this has yet to be investigated in detail. 

The Australian Dental Association recommends regular oral hygiene appointments and dental health checks, in addition to twice daily teeth brushing and flossing.  

Bad breath, bad news: how gum disease could worsen liver conditions

 

 

Caption

Oral and gut microflora associated with healthy states and dysbiosis.

Credit

By David Hudson, Gustavo Ayares, Zahra Taboun, et al.

Peer-Reviewed Publication

First Hospital of Jilin University

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

Oral and gut microflora associated with healthy states and dysbiosis.

view more 

Credit: By David Hudson, Gustavo Ayares, Zahra Taboun, et al.

There is growing recognition in medicine that what happens in one part of the body can ripple through others. That idea is now being explored in a surprising place: the mouth. A new review by an international group of researchers has examined the mounting evidence linking periodontal disease—commonly known as gum disease—to chronic liver conditions, including cirrhosis, metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-related liver disease. Though the mouth and liver are separated by both distance and function, the paper makes a compelling case that these two systems are more connected than we thought.

Gum disease, especially in its more advanced form known as periodontitis, is a chronic inflammatory condition caused by bacterial infections in the tissues that support the teeth. It is one of the most common diseases worldwide, and its severity tends to increase with age, smoking, alcohol use, and poor access to dental care. For patients already struggling with liver disease—many of whom share these same risk factors—oral health often takes a back seat.

But ignoring the mouth could be a mistake. The review lays out multiple ways that periodontitis may aggravate liver disease. The first is via the "oral-gut-liver axis," a term researchers use to describe the complex interplay between oral bacteria, the gut microbiome, and liver function. Pathogenic bacteria from the mouth can be swallowed or enter the bloodstream during everyday activities like chewing and brushing. Once in the gut, these microbes may alter the composition of the intestinal microbiome, leading to dysbiosis and increased gut permeability—also known as a "leaky gut." This can allow bacterial products such as endotoxins to reach the liver, triggering inflammation and fibrogenesis.

Animal models offer further support for this theory. Studies have shown that oral administration of specific periodontal pathogens, such as Porphyromonas gingivalis, can exacerbate liver steatosis and inflammation in mice with pre-existing metabolic disease. These microbes, or their byproducts, have even been found in liver tissue, suggesting that translocation from the mouth to the liver is biologically plausible.

The immune system also plays a central role in this interaction. Chronic periodontal inflammation leads to the release of pro-inflammatory cytokines like TNF-alpha and IL-6, which have long been implicated in the progression of liver disease. Additionally, the review highlights the involvement of Th17 cells—a type of immune cell activated by oral pathogens that may migrate to the liver and worsen metabolic dysfunction. Together, these pathways form a vicious cycle: liver disease impairs oral health, while oral inflammation accelerates liver damage.

The clinical data, while still developing, supports this association. Patients with cirrhosis consistently show worse oral health than the general population, with higher rates of gingival overgrowth, attachment loss, and bone loss. The prevalence of periodontitis among patients awaiting liver transplantation can be as high as 72 percent. Studies have also found links between severe periodontal disease and increased mortality in cirrhosis patients.

For those with MASLD, the most common form of chronic liver disease, the evidence is also compelling. Population-level studies have found that people with advanced periodontitis are significantly more likely to have MASLD, even after adjusting for shared risk factors like obesity and diabetes. And in a small trial, periodontal treatment led to a short-term improvement in liver enzyme levels—a tantalizing hint that oral health interventions could influence liver function.

That said, the review authors caution that the research is still at an early stage. Much of the clinical data comes from observational studies, which cannot definitively prove cause and effect. There is also the challenge of disentangling shared lifestyle and socioeconomic factors that affect both oral and liver health. Still, the biological plausibility, consistency of findings, and preliminary interventional data make a strong case for paying more attention to the teeth and gums of patients with liver disease.

The review ends with a call for multidisciplinary collaboration. Gastroenterologists and hepatologists, who typically manage liver disease, may not think to ask about oral health or refer patients for dental care. Yet the data suggest they should. Similarly, dental professionals may not be aware of how their work could influence liver outcomes. Closer cooperation between these specialties could lead to earlier detection and better care.

Until more definitive evidence is available, one message is clear: brushing, flossing, and regular dental visits might be more important than we ever realized, especially for those living with chronic liver conditions. In the meantime, researchers are calling for larger, high-quality trials to test whether treating gum disease can slow liver disease progression or reduce complications. If the connection holds, the humble toothbrush could become an unexpected tool in the fight against liver failure.

An antiviral chewing gum to reduce influenza and herpes simplex virus transmission

Researchers at Penn Dental Medicine and collaborators have used a clinical-grade antiviral chewing gum to substantially reduce viral loads of two herpes simplex viruses and two influenza A strains in experimental models

Peer-Reviewed Publication

University of Pennsylvania

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

 

image: 

The engineering and evaluation of anti-viral bean gum.

view more 

Credit: Yuwei Guo, Rachel Kulchar, Rahul Singh, and Geetanjali Wakade

In today’s interconnected world, infectious diseases pose an escalating threat, as demonstrated by the coronavirus pandemic and outbreaks of H1N1, SARS, Ebola, Zika, and H5N1 (bird flu) viruses—all of which have had significant global health and economic impacts.

But more common viral diseases also contribute to global health challenges and economic costs. For example, seasonal influenza epidemics occur annually, causing a substantial global disease burden and economic losses exceeding $11.2 billion each year in the United States alone. Meanwhile, herpes simplex virus-1 (HSV-1), spread primarily through oral contact, infects over two-thirds of the global population and is the leading cause of infectious blindness in Western countries.

Low vaccination rates for influenza viruses and the lack of an HSV vaccine underscore the need for a new approach—one that targets reducing viral loads at the sites where transmission occurs. And for viruses like these, which are transmitted more efficiently through the mouth than the nose, this means focusing on the oral cavity.

Now, in a study published in Molecular Therapy, researchers at the School of Dental Medicine at the University of Pennsylvania and collaborators in Finland, have done just that.

Building on their previous work—now in clinical trial—showing that a similar approach was able to reduce SARS-CoV-2 in COVID-19 patient saliva or swab samples by more than 95%, Henry Daniell, W.D. Miller Professor in Penn’s School of Dental Medicine, and collaborators tested the ability of a chewing gum made from lablab beans, Lablab purpureus—that naturally contain an antiviral trap protein (FRIL)—to neutralize two herpes simplex viruses (HSV-1 and HSV-2) and two influenza A strains (H1N1 and H3N2). The chewing gum formulation allowed for effective and consistent release of FRIL at sites of viral infection. 

They demonstrated that 40 milligrams of a two-gram bean gum tablet was adequate to reduce viral loads by more than 95%, a reduction similar to what they saw in their SARS-CoV-2 study.

Importantly, the researchers prepared the gum as a clinical-grade drug product to comply with the FDA specifications for drug products and found the gum to be safe. Daniell notes, “These observations augur well for evaluating bean gum in human clinical studies to minimize virus infection/transmission.”

Daniell and his colleagues are now looking to use lablab bean powder to tackle bird flu, which is currently having a significant impact in North America. In the previous three months, 54 million birds have been affected by H5N1, and several human infections have been reported in the U.S. and Canada.

Previously, bean powder was shown by others to effectively neutralize H5N1 and H7N9—two strains of influenza A known to cause bird flu in humans as well as in birds. Daniell and colleagues are currently looking to test its use in bird feed to help control bird flu in birds.

“Controlling transmission of viruses continues to be major global challenge. A broad spectrum antiviral protein (FRIL) present in a natural food product (bean powder) to neutralize not only human flu viruses but also avian (bird) flu is a timely innovation to prevent their infection and transmission,” says Daniell.

Henry Daniell is the W.D. Miller Professor in the Department of Basic & Translational Sciences at the School of Dental Medicine at the University of Pennsylvania.

Other authors include Gary H. Cohen, Yuwei Guo, Uddhab Karki, Rachel J. Kulchar, Rahul Singh, and Geetanjali Wakade of Penn Dental Medicine, Hamid Khazaei of the Natural Resources Institute Finland (Luke) and the University of Finland and Juha-Matti Pihlava of the University of Finland.

Research performed in the Daniell lab is supported by NIH grant R01 HL 107904.

Study links lack of oral health care with complications during pregnancy

For pregnant women in the U.S., the use of oral health services during pregnancy remains low, with fewer than 40% seeking preventive oral health care. So reports a new study conducted by the Oral Health Workforce Research Center, part of the Center for Health Workforce Studies at the University at Albany’s College of Integrated Health Sciences, which was featured on the cover of this month’s issue of the Journal of the American Dental Association.

UAlbany researchers analyzed data from the Pregnancy Risk Assessment Monitoring System (PRAMS), a longstanding data repository maintained by the Centers for Disease Control and Prevention, between 2016 and 2020. Disparities in gestational diabetes and hypertensive disorders were highlighted, with higher odds of these pregnancy complications among lower-income and minority women. 

Lack of regular preventive oral health care and delaying dental treatment during pregnancy increases the risk of developing dental diseases such as periodontal disease, which is potentially associated with gestational diabetes and hypertensive disorders.

The research team found that pregnant women who received preventive oral health care or visited a dentist or a dental clinic for oral health problems during pregnancy did in fact have a lower risk of developing gestational diabetes and hypertensive disorders.

“Our findings reinforce the connection between oral health and overall health,” said Dr. Simona Surdu, project director at the Center for Health Workforce Studies. “Integrating oral health education and services into maternal health care and expanding the oral health workforce through training, better distribution and interprofessional collaboration with prenatal care providers can improve access to oral health services for pregnant women — especially in underserved populations — and help reduce the risks of gestational diabetes and hypertensive disorders.” 

 

Pandemic dental office closures linked to increased burden on ERs from kids with dental issues

 

A lack of access to dentists during the COVID-19 pandemic coincided with a surge in hospital visits for dental conditions among Medicaid-insured children

Peer-Reviewed Publication

New York University

FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

Dental office closures early in the COVID-19 pandemic were associated with a 62-percent increase in the share of emergency department visits from toothaches, abscesses, and other painful dental issues among children covered by Medicaid, according to a new study led by researchers at NYU College of Dentistry.

The findings, published in the Journal of the American College of Emergency Physicians Open, suggest that families with young kids have difficulty accessing dental care during public health crises, which may further stress overburdened hospitals.

In March 2020, as COVID-19 cases grew exponentially in New York and around the country, public health measures to stop the virus’s spread prompted the closure of dental offices. While dentists could see patients for emergency appointments, all other routine dental care was postponed.

At the same time, hospitals were filling up with critically ill patients. NYU researchers wanted to understand whether patients with urgent dental issues were also ending up in emergency rooms.

“Emergency departments are not well equipped to treat dental conditions, as they are typically limited to relieving pain and referring patients to dentists to address the underlying issues,” said Shulamite Huang, a health economist and assistant professor of epidemiology and health promotion at NYU College of Dentistry. “As a result, visiting an emergency department for tooth pain can be a waste of health care system resources—resources that are in short supply during times of crisis, including the peak of the COVID-19 pandemic.”

Huang and her colleagues examined Medicaid claims data for children under the age of 19 across New York State to determine if there were any differences in emergency department visits for dental concerns before the pandemic (in 2018 and 2019) versus 2020. They focused on issues including cavities, infections, and abscesses, and excluded injuries such as cracked or knocked-out teeth.

The researchers found that denta practice closures from March through May 2020 led to a 62- percent increase in the share of children’s emergency room visits from non-traumatic dental issues over 2019 levels (from 3.7 percent of ER visits focusing on dental issues in 2019 to 6 percent in 2020). This surge in visits was the most pronounced among young children up to age 9, who were seen in emergency departments for dental issues twice as often during this period compared to the previous year.

Notably, the increase in emergency department visits was sustained even after many dentists reopened their offices in May 2020, although to a lesser degree.

“The sizable changes in the emergency department dental care of very young children suggests that this population was likely to fall through holes in the dental safety net,” said Huang. “Although dentists were allowed to treat dental emergencies, Medicaid-insured children may have had difficulty accessing care during the initial phase of the COVID-19 pandemic.”

The authors cite several possible reasons for this, including parents having difficulty determining whether kids in pain are experiencing a true emergency. In addition, very young children covered by Medicaid may not have established care with a dentist before the pandemic, as finding a dentist that accepts Medicaid and treats young children can be a challenge.

In preparation for future pandemics or other crises that stress US hospitals, the researchers encourage health systems to consider options for emergency dental care that can divert patients from the emergency department, including offering limited hospital-based dental services or incorporating urgent dental care clinics within hospitals. In addition, ensuring that children covered by Medicaid have access to a dentist in their community may both prevent painful dental issues and provide them with emergency dental care when needed.

Additional study authors include Scarlett Wang of the NYU Wagner Graduate School of Public Service and Heather Gold of NYU Grossman School of Medicine. This research was supported by the National Institute of Dental and Craniofacial Research (K25 DE028584 and K25 DE028584-02S1). 

---

Journal

Journal of the American College of Emergency Physicians Open

DOI

10.1016/j.acepjo.2025.100094