New drug to regenerate lost teeth

The tooth fairy is a welcome guest for any child who has lost a tooth. Not only will the fairy leave a small gift under the pillow, but the child can be assured of a new tooth in a few months. The same cannot be said of adults who have lost their teeth.

A new study by scientists at Kyoto University and the University of Fukui, however, may offer some hope. The team reports that an antibody for one gene -- uterine sensitization associated gene-1 or USAG-1 -- can stimulate tooth growth in mice suffering from tooth agenesis, a congenital condition. The paper was published in Science Advances.

Although the normal adult mouth has 32 teeth, about 1% of the population has more or fewer due to congenital conditions. Scientists have explored the genetic causes for cases having too many teeth as clues for regenerating teeth in adults.

According to Katsu Takahashi, one of the lead authors of the study and a senior lecturer at the Kyoto University Graduate School of Medicine, the fundamental molecules responsible for tooth development have already been identified.

"The morphogenesis of individual teeth depends on the interactions of several molecules including BMP, or bone morphogenetic protein, and Wnt signaling," says Takahashi.

BMP and Wnt are involved in much more than tooth development. They modulate the growth of multiple organs and tissues well before the human body is even the size of a raisin. Consequently, drugs that directly affect their activity are commonly avoided, since side effects could affect the entire body.

Guessing that targeting the factors that antagonize BMP and Wnt specifically in tooth development could be safer, the team considered the gene USAG-1.

"We knew that suppressing USAG-1 benefits tooth growth. What we did not know was whether it would be enough," adds Takahashi.

The scientists therefore investigated the effects of several monoclonal antibodies for USAG-1. Monoclonal antibodies are commonly used to treat cancers, arthritis, and vaccine development.

USAG-1 interacts with both BMP and Wnt. As a result, several of the antibodies led to poor birth and survival rates of the mice, affirming the importance of both BMP and Wnt on whole body growth. One promising antibody, however, disrupted the interaction of USAG-1 with BMP only.

Experiments with this antibody revealed that BMP signaling is essential for determining the number of teeth in mice. Moreover, a single administration was enough to generate a whole tooth. Subsequent experiments showed the same benefits in ferrets.

"Ferrets are diphyodont animals with similar dental patterns to humans. Our next plan is to test the antibodies on other animals such as pigs and dogs," explains Takahashi.

The study is the first to show the benefits of monoclonal antibodies on tooth regeneration and provides a new therapeutic framework for a clinical problem that can currently only be resolved with implants and other artificial measures.

"Conventional tissue engineering is not suitable for tooth regeneration. Our study shows that cell-free molecular therapy is effective for a wide range of congenital tooth agenesis," concludes Manabu Sugai of the University of Fukui, another author of the study.

Study Ties Gum Disease to High Blood Pressure

A new study finds that severe gum disease may make an otherwise healthy person significantly more likely to develop high blood pressure.

"[Our] evidence indicates that periodontal bacteria cause damage to the gums and also triggers inflammatory responses that can impact the development of systemic diseases including" high blood pressure, said study author Dr. Francesco D'Aiuto, head of the periodontology unit at University College London Eastman Dental Institute. He spoke in a news release from the journal Hypertension, which published the report March 29.

The researchers studied 250 otherwise healthy adults with severe periodontitis and 250 healthy adults without the gum disease. Their median age was 35, meaning half were older, half younger.

Participants with gum disease were twice as likely to have high systolic blood pressure (140 mm Hg or more), than those with healthy gums (14% and 7%, respectively), according to the findings. The systolic level -- top number in a blood pressure reading -- is how much pressure your blood is exerting on your blood vessels as it moves through the body.

While only an association and not a cause-and-effect link was established, the findings suggest that about 50% of adults could have undetected high blood pressure due to gum disease -- a tissue infection that can also lead to inflammation and bone or tooth loss.

Researchers said preventing and treating gum disease may be a cost-effective way to reduce systemic inflammation and improve function of the endothelium, the thin lining inside the heart and blood vessels.

"Patients with gum disease often present with elevated blood pressure, especially when there is active gingival inflammation, or bleeding of the gums," said lead author Dr. Eva Muñoz Aguilera, senior researcher at the institute.

Because high blood pressure often has no outward symptoms, many individuals may be unaware that they are at increased risk for heart-related problems, she added in the release.

Having dental professionals screen for high blood pressure and make referrals to primary care providers while medical professionals also screen and refer for gum disease could benefit patients' health and reduce the burden of high blood pressure and its complications, according to D'Aiuto.

"Oral health strategies such as brushing teeth twice daily are proven to be very effective in managing and preventing the most common oral conditions, and our study's results indicate they can also be a powerful and affordable tool to help prevent hypertension," D'Aiuto concluded.

Study offers new insights into dental caries development and prevention

HONG KONG, China/BERKELEY, Calif., US: A study led by researchers in China has recently examined the impact of the oral microbiota on overall health. The researchers found that a novel microbial small molecule released by Streptococcus mutans, a bacterium commonly found in the human oral cavity, is linked to dental caries development. With its new insights, the study could help scientists undertaking new research to find a way to prevent dental caries.

Dental caries is an age-old dilemma that continues to pose a threat to our oral and overall health. According to the World Health Organization, approximately 2.3 billion people suffer from caries of permanent teeth, and more than 530 millionchildren suffer from caries of primary teeth globally. The organisation also noted that the prevalence of oral disease continues to increase in most low- and middle-income countries, where the population is increasingly shifting to urban areas and experiencing changes in living conditions.

Dental Tribune International (DTI) has previously reported that taking some unusual measures, such as eating Chinese pickles or berry extract or using dual-light photodynamic therapy, could help prevent the disease. But how much do we know about the actual culprit behind dental caries?

In the present study, the researchers examined biofilm formation by a bacterium S. mutans, which produces organic acids and is one of the main causes of dental caries. “S. mutans has long been recognised as one of the major oral pathogens, and genomic sequencing of various clinical isolates has revealed a great potential to produce specialised secondary metabolites,” co-author Dr Wenjun Zhang, associate professor in the Department of Chemical and Biomolecular Engineering at the University of California, Berkeley, told DTI.

Although scientists have previously extensively investigated the macromolecular agents of S. mutans that are responsible for biofilm formation and development, the identity and function of small-molecule secondary metabolites in biofilm formation by S. mutans remains largely unknown. Therefore, the researchers aimed to fill this gap.

“I have been studying the interaction of marine natural biofilm and marine animals for many years. As such interaction is often mediated via chemical molecules produced by microbes in biofilm, one of our efforts is to identify the molecules that affect biofilm development as well as the animals’ response,” explained co-author Dr Peiyuan Qian, head and chair professor of the Department of Ocean Science at the Hong Kong University of Science and Technology.

“Over the last ten years, we have been using genome mining-based compound discovery to identify chemical signals from microbes and we have made some breakthroughs, such as identifying genotoxins (colibactins) from E. coli, developing new antibiotics and finding new drug leads,” he continued.

“If we can prevent biofilm-forming bacteria from producing the relevant molecules, we can prevent the formation of dental plaque”

— Dr Peiyuan Qian, HKUST

Owing to a common interest in the molecular mechanisms of biofilm development, Qian and his team has been working closely with Zhang over the last few years. As he explained, the collaboration was a logical step. “It is a natural extension of our work to go from marine natural biofilm to biofilm associated with human health,” he explained.

In the course of their study, the researchers identified five molecules and a biosynthetic pathway gene cluster. According to the findings, one of the molecules was found to latch onto S. mutans and reduced the bacterial cells’ attraction to water molecules, thus promoting the cells’ ability to form clumps. “We discovered that some isolates of S. mutans are capable of producing a specialised metabolite, mutanofactin-697. This molecule binds to S. mutans cells and also to extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation,” Zhang explained.

Talking about the importance of the findings, Qian explained that the study could greatly contribute to the prevention of dental caries. He noted: “Bacteria sheltered in a biofilm in the dental plaque can unleash large amounts of acid that attack tooth enamel. If we can prevent biofilm-forming bacteria from producing the relevant molecules, we can prevent the formation of dental plaque.”

School-based Dental Program Reduces Cavities by More than 50 Percent

A school-based cavity prevention program involving nearly 7,000 elementary school students reduced cavities by more than 50 percent, according to a study led by researchers at NYU College of Dentistry. The findings are published March 1 in the Journal of the American Dental Association.

“The widespread implementation of oral health programs in schools could increase the reach of traditional dental practices and improve children’s oral health—all while reducing health disparities and the cost of care,” said Richard Niederman, DMD, professor and chair of the Department Epidemiology & Health Promotion at NYU College of Dentistry and the study’s senior author.

Dental cavities are the most common chronic disease in children, and one in five elementary school children have at least one untreated cavity. While cavities can be prevented with dental visits and good at-home oral hygiene, some families experience barriers to seeing a dentist, including cost and parents having to take time off of work.

“School-based cavity prevention programs eliminate these barriers by bringing basic dental care to children, rather than bringing children to care,” said Niederman.

The study was conducted in 33 public, high-need elementary schools in Massachusetts, where dental hygienists provided care to 6,927 children. The services were provided at no cost to families.

Twice-yearly visits involved dental examinations followed by cavity prevention and treatment, including fluoride varnish, sealants, and minimally invasive fillings to stabilize cavities without drilling. Students also received oral hygiene instructions, toothbrushes, and fluoride toothpaste to take home. If more complex care was required, students were referred to local dentists. Notably, the procedures used do not create aerosols, which limits the risk of transmitting viruses through the air.

After six visits, the prevalence of untreated cavities decreased by more than 50 percent. In one group of schools, cavities were reduced from a baseline of 39 percent to 18 percent, and in a second group, cavities decreased from 28 percent to 10 percent. The prevention program reduced cavities in both baby and permanent teeth.

“In 2010, the federal government set a goal of reducing the prevalence of cavities in children by 10 percent by 2020. Our study shows that this is not only feasible, but also that a comprehensive school-based program can reduce cavities by five times their goal,” said Niederman.

Recent economic analyses of school-based cavity prevention programs by researchers at NYU College of Dentistry, including one focusing on this program in Massachusetts, demonstrate that they are cost-effective and could save federal dollars. If this school-based program was implemented nationally, it could reduce Medicaid spending on children’s oral health by as much as one-half.

The COVID-19 pandemic has interrupted most school-based dental care because of school closures and fear of creating aerosols, even as oral health care in dental practices has safely resumed with additional infection control measures in place. The researchers stress the importance of safely continuing school-based care, given its ability to prevent cavities using aerosol-free procedures.

In addition to Niederman, study authors include Jacqueline Starr of Brigham and Women's Hospital, Ryan Ruff of NYU Dentistry, Joseph Palmisano of Boston University School of Public Health, Max Goodson of the Forsyth Institute, and Omair Bukhari of Umm Alqura University in Saudi Arabia. The research was supported by the National Institute on Minority Health and Health Disparities, part of the National Institutes of Health (U24MDD006964), as well as DentaQuest, Bingham Trust, the Massachusetts State Legislature, and the American Dental Trade Alliance. Dental supplies were provided by GC America and Colgate-Palmolive.

About NYU College of Dentistry

Founded in 1865, New York University College of Dentistry (NYU Dentistry) is the third oldest and the largest dental school in the US, educating nearly 10 percent of all dentists. NYU Dentistry has a significant global reach with a highly diverse student body. Visit dental.nyu.edu for more.

Bleeding Gums? You Might Be Lacking Vitamin C

If you have bleeding gums, you may need to increase the amount of vitamin C in your diet, a new study suggests.

The American Dental Association says bleeding could be a sign of gingivitis, an early stage of gum disease. These new findings from University of Washington (UW) researchers suggest you should also check your vitamin C intake.

"When you see your gums bleed, the first thing you should think about is not, I should brush more. You should try to figure out why your gums are bleeding. And vitamin C deficiency is one possible reason," said study lead author Dr. Philippe Hujoel. He's a dentist and professor of oral health sciences at the UW School of Dentistry, in Seattle.

For the study, the researchers analyzed results of 15 clinical trials from six countries that included more than 1,100 participants, and data from more than 8,200 participants in the U.S. National Health and Nutrition Examination Survey.

Bleeding of the gums on gentle probing and bleeding in the eye (retinal bleeding) were associated with low vitamin C levels in the blood, and boosting daily intake of vitamin C helped reverse those issues, according to findings published Feb. 1 in the journal Nutrition Reviews. Both gum bleeding and retinal bleeding could be signs of a microvascular bleeding tendency in the brain, heart and kidneys, Hujoel noted.

But these findings don't suggest that reversing gum bleeding by increasing vitamin C intake will prevent stroke or other serious outcomes, he stressed.

The findings do indicate that vitamin C recommendations designed primarily to protect against scurvy -- a deadly disease caused by extremely low vitamin C levels -- are too low. These levels can lead to gum bleeding.

Hujoel said people should get sufficient vitamin C intake by eating non-processed foods such as kale, peppers or kiwis. If you can't find vitamin C-rich foods that you like, consider a supplement of about 100 to 200 milligrams a day, he advised.

Why Cavemen Needed No Braces

Modern industrialized societies are plagued by crowded, ill-aligned teeth, a condition that the dental profession refers to as “malocclusion”—which translates literally to “bad bite.” Survey data from 1998 suggests that as much as a fifth of the U.S. population has significant malocclusion, over half of which require at least some degree of orthodontic intervention. Braces, tooth extractions, and retainers are the bread and butter for all the dentists and orthodontists tasked with setting straight our dental deviations. Having braces as a child has become so common in the Western world that it can seem a rite of passage—today, an estimated 50 to 70 percent of U.S. children will wear braces before adulthood. But what did humans do to fix their teeth before modern dentistry, before Novocain, gauze, and rubber spacers?

As it turns out, our ancestors did not suffer from crooked teeth to the same extent that we do today. Our species’ fossil record reveals a telling story: the epidemic of crooked teeth developed in humans over time. Evolutionary biologist, Daniel Lieberman, notes the pattern in his book, The Story of the Human Body:

Ample evidence abounds in support of Lieberman’s observations. A comparison of 146 medieval skulls from abandoned Norwegian graveyards with modern skulls indicated a trend toward bad bite in our more recent forebears. The skulls of people scored as being in “great” or “obvious” need of orthodontic treatment made up 36 percent of the medieval sample and 65 percent of the modern sample. And evidence of malocclusion in still earlier human fossils is vanishingly rare. The jaws of hunter-gatherers nearly uniformly reveal roomy, perfect arches of well aligned teeth, with no impacted wisdom teeth—a movie star’s dream smile, 15,000 years before the movies!

FDA Clears Novel Daytime Device for Obstructive Sleep Apnea

The US Food and Drug Administration (FDA) has approved the first device to help reduce snoring and mild obstructive sleep apnea (OSA) that is used during the day while the patient is awake.

eXciteOSA (Signifier Medical Technologies, LLC) is a prescription-only, neuromuscular stimulation device designed to improve tongue muscle function, which, over time, can help prevent the tongue from collapsing backwards and obstructing the airway during sleep, the FDA said.

The eXciteOSA mouthpiece has four electrodes that deliver a series of electrical pulses with rest periods in between. Two electrodes are located above the tongue and two are located below the tongue.

The patient uses the device for 20 minutes once a day while awake for 6 weeks, and once a week thereafter. It is indicated for adults aged 18 and older with snoring and mild OSA.

OSA is marked by the recurring collapse of the upper airways during sleep, intermittently reducing or completely blocking airflow. Common symptoms include snoring, restless sleep and daytime sleepiness. Untreated OSA can lead to serious complications such as cardiovascular disease and cognitive and behavioral disorders.

Continuous positive airway pressure (CPAP) therapy, administered through a facemask that is worn while asleep, is a first-line treatment for OSA.

The eXciteOSA device "offers a new option for the thousands of individuals who experience snoring or mild sleep apnea," Malvina Eydelman, MD, director, FDA Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices, said in a news release.

The FDA reviewed data on the safety and effectiveness of the eXciteOSA device in 115 patients with snoring, including 48 patients with snoring and mild OSA. All patients used the device for 20 minutes once a day for 6 weeks, then stopped using it for 2 weeks before they were reassessed.

Overall, the percentage of time spent snoring at levels louder than 40 decibels (dB) was reduced by more than 20% in 87 out of the 115 patients.

In the subset of patients with snoring and mild OSA, the average apnea-hypopnea index (AHI) score was reduced by 48%, from 10.21 to 5.27, in 41 of 48 patients. Mild OSA is defined as an AHI score greater than 5 but less than 15.

The most common adverse events were excessive salivation, tongue or tooth discomfort, tongue tingling, dental filling sensitivity, metallic taste, gagging, and tight jaw.

Before using the eXciteOSA device, patients should receive a comprehensive dental examination, the FDA says.

The device should not be used in patients with pacemakers or implanted pacing leads, or women who are pregnant. The device is also contraindicated in patients with temporary or permanent implants, dental braces, intraoral metal prosthesis/restorations, or ulcerations in or around the mouth.

The eXciteOSA device was approved under the de novo premarket review pathway for new low- to moderate-risk devices. More information on the device is available online.

How Can Exercise Improve Oral Health?

Exercise has so many documented benefits, including its ability to lower the risk of heart disease, obesity, Type 2 diabetes, and some types of cancer – but research indicates it can also boost oral health. One study published in the Journal of Dentistry showed that regular physical activity can boost periodontal health. To be more precise, people who exercised regularly had a 54% lower likelihood of developing periodontitis compared to those who led sedentary lives. The National Health and Nutrition Examination Survey additionally revealed that people who exercised three times a week or less could also reap benefits, which means they have a 33% lower likelihood of developing periodontitis.

Bleeding gums may be a sign you need more vitamin C in your diet

Current advice from the America Dental Association tells you that if your gums bleed, make sure you are brushing and flossing twice a day because it could be a sign of gingivitis, an early stage of periodontal disease. And that might be true. So if you are concerned, see your dentist. However, a new University of Washington study suggests you should also check your intake of vitamin C.

"When you see your gums bleed, the first thing you should think about is not, I should brush more. You should try to figure out why your gums are bleeding. And vitamin C deficiency is one possible reason," said the study's lead author Philippe Hujoel, a practicing dentist and professor of oral health sciences in the UW School of Dentistry.

Hujoel's study, published Feb. 1 in Nutrition Reviews, analyzed published studies of 15 clinical trials in six countries, involving 1,140 predominantly healthy participants, and data from 8,210 U.S. residents surveyed in the Centers for Disease Control and Prevention's Health and Nutrition Examination Survey. The results showed that bleeding of the gums on gentle probing, or gingival bleeding tendency, and also bleeding in the eye, or retinal hemorrhaging, were associated with low vitamin C levels in the bloodstream. And, the researchers found that increasing daily intake of vitamin C in those people with low vitamin C plasma levels helped to reverse these bleeding issues.

Of potential relevance, says Hujoel, who is also an adjunct professor of epidemiology in the UW School of Public Health, both a gum bleeding tendency and retinal bleeding could be a sign of general trouble in one's microvascular system, of a microvascular bleeding tendency in the brain, heart and kidneys.

The study does not imply that successful reversing of an increased gingival bleeding tendency with vitamin C will prevent strokes or other serious health outcomes, Hujoel stresses. However, the results do suggest that vitamin C recommendations designed primarily to protect against scurvy -- a deadly disease caused by extremely low vitamin C levels -- are too low, and that such a low vitamin C intake can lead to a bleeding tendency, which should not be treated with dental floss.

Consequently, Hujoel does recommend people attempt to keep an eye on their vitamin C intake through incorporation of non-processed foods such as kale, peppers or kiwis into your diet, and if you can't find palatable foods rich in vitamin C to consider a supplement of about 100 to 200 milligrams a day.

If someone is on a specialized diet, such as a paleo diet, it's important that they take a look at their vitamin C intake, Hujoel said. "Vitamin C-rich fruits such as kiwis or oranges are rich in sugar and thus typically eliminated from a low-carb diet."

This avoidance may lead to a vitamin C intake that is too low and is associated with an increased bleeding tendency. People who exclusively eat lean meats and avoid offal, the vitamin-rich organ meats, may be at a particularly high risk for a low vitamin C intake.

The association between gum bleeding and vitamin C levels was recognized more than 30 years ago. In fact, two studies co-authored by former dean of the UW School of Dentistry Paul Robertson (published in 1986 and 1991) identified gum bleeding as a biological marker for vitamin C levels.

However, this connection somehow got lost in dental conversations around bleeding gums.

"There was a time in the past when gingival bleeding was more generally considered to be a potential marker for a lack of vitamin C. But over time, that's been drowned out or marginalized by this overattention to treating the symptom of bleeding with brushing or flossing, rather than treating the cause," Hujoel said.

Hujoel's literature review also determined that "retinal hemorrhaging and cerebral strokes are associated with increased gingival bleeding tendency, and that (vitamin C) supplementation reverses the retinal bleeding associated with low (vitamin C) plasma levels."

So, missing the possible connection between gum bleeding and low levels of vitamin C has the potential to have serious health consequences.

The study authors write: "A default prescription of oral hygiene and other periodontal interventions to 'treat' microvascular pathologies, even if partially effective in reversing gingival bleeding as suggested in this meta-analysis, is risky because it does not address any potential morbidity and mortality associated with the systemic microvascular-related pathologies.’

Researchers demonstrate how changing the stem cell response to inflammation may reverse periodontal disease

Periodontal disease, also known as gum disease, is a serious infection that affects nearly 50 percent of Americans aged 30 years and older. If left unchecked, periodontal disease can destroy the jawbone and lead to tooth loss. The disease is also associated with higher risk of diabetes and cardiovascular disease.

The current treatment for periodontal disease involves opening the infected gum flaps and adding bone grafts to strengthen the teeth. But in new research published recently in the journal Frontiers in Immunology, Forsyth Institute scientists have discovered that a specific type of molecule may stimulate stem cells to regenerate, reversing the inflammation caused by periodontal disease. This finding could lead to the development of new therapeutics to treat a variety of systemic diseases that are characterized by inflammation in the body.

For the study, Dr. Alpdogan Kantarci, his PhD student Dr. Emmanuel Albuquerque, and their team removed stem cells from previously extracted wisdom teeth and placed the stem cells onto petri dishes. The researchers then created a simulated inflammatory periodontal disease environment in the petri dishes. Next, they added two specific types of synthetic molecules called Maresin-1 and Resolvin-E1, both specialized pro-resolving lipid mediators from omega-3 fatty acids. The scientists found that Mar1 and RvE1 stimulated the stem cells to regenerate even under the inflammatory conditions.

"Both Maresin-1 and Resolvin-1 reprogrammed the cellular phenotype of the human stem cells, showing that even in response to inflammation, it is possible to boost capacity of the stem cells so they can become regenerative," said Dr. Kantarci, Associate Member of Staff at the Forsyth Institute.

This finding is important because it allows scientists to identify the specific protein pathways involved in inflammation. Those same protein pathways are consistent across many systemic diseases, including periodontal disease, diabetes, heart disease, dementia, and obesity.

"Now that we understand how these molecules stimulate the differentiation of stem cells in different tissues and reverse inflammation at a critical point in time, the mechanism we identified could one day be used for building complex organs" said Dr. Kantarci. "There is exciting potential for reprogramming stem cells to focus on building tissues."