Can We Regrow Teeth? The Science of Tooth Regeneration

The Science of Tooth Regeneration

Quick answer: Yes—tooth regeneration is moving from theory toward reality. Researchers have shown that blocking a protein called USAG-1 with a neutralizing antibody can regrow teeth in mice and ferrets by reactivating the body’s dormant “third dentition.” A USAG-1-targeting drug entered Phase I human trials in 2024, offering hope for people with congenital tooth agenesis and, eventually, adult tooth loss.

Losing a tooth as a child feels almost magical—a new one grows in to replace it. Lose a tooth as an adult, and your only options are implants, bridges, or dentures. None of these restore a real, living tooth.

That may be about to change. A 2023 review published in Regenerative Therapy by Ravi, Murashima-Suginami, Kiso, and colleagues (Ravi et al., 2023) maps out how scientists are learning to regrow teeth from a person’s own tissue. The work centers on a protein called USAG-1 and a striking idea: humans may carry the hidden potential for a third set of teeth.

This post breaks down where the science stands—what causes missing teeth, the genes involved, and how a single antibody could unlock natural tooth growth.

What is tooth agenesis, and how is it classified?

Tooth agenesis is the failure of one or more teeth to develop. It is one of the most common congenital conditions affecting humans, and dentists classify it by how many teeth are missing.

• Hypodontia: fewer than six missing teeth, excluding third molars (wisdom teeth). This is the mildest and most common form.
• Oligodontia: six or more missing teeth, excluding third molars. This is more severe and often linked to genetic syndromes.
• Anodontia: the complete absence of teeth, which is rare.

Missing teeth are not just a cosmetic concern. They can disrupt chewing, speech, and jaw development, and they frequently appear alongside conditions such as cleft lip and cleft palate. About 1% of the population has more or fewer than the standard 32 teeth due to congenital factors.

Which genes cause tooth agenesis?

Tooth development is a tightly choreographed process driven by signals passing between two tissues: the dental epithelium and the dental mesenchyme. When the genes controlling these signals carry mutations, teeth may fail to form.

Several genes are strongly linked to tooth agenesis:

• WNT10A: Variants in this gene are the most frequent genetic cause of isolated hypodontia and oligodontia, usually inherited in an autosomal recessive pattern.
• MSX1 and PAX9: These transcription factors are essential for early tooth formation. Mutations often cause missing molars and premolars.
• EDA: Linked to tooth agenesis that appears alongside ectodermal dysplasia, a condition affecting hair, skin, and sweat glands.
• AXIN2: Associated with oligodontia and an increased risk of colorectal cancer.
• LTBP3 and TP63: Additional genes connected to syndromic forms of missing teeth.

These genes feed into two master signaling pathways—BMP (bone morphogenetic protein) and Wnt. Both pathways do far more than build teeth; they guide the growth of organs throughout the body. That wide reach is exactly why directly manipulating BMP or Wnt is risky, and why researchers needed a more precise target.

What is the “third dentition,” and could humans grow a third set of teeth?

Most mammals, including humans, are diphyodont—we grow two sets of teeth, baby teeth and permanent teeth. But evidence suggests the body may hold the blueprint for a third set.

During development, the mouth forms more tooth buds than it ultimately uses. Many of these extra “tooth germs” are suppressed before they can develop. The idea of the third dentition is that these dormant buds could be reactivated to grow new teeth—if scientists can release the molecular brakes holding them back.

This is where USAG-1 enters the picture. USAG-1 (Uterine Sensitization Associated Gene-1) acts as one of those brakes. In normal development, USAG-1 limits tooth formation by suppressing extra tooth germs. Remove it, and the suppressed teeth get a chance to emerge.

What did USAG-1 knockout research in mice reveal?

The case for USAG-1 as a target became clear through experiments in genetically modified mice.

USAG-1 inhibits BMP signaling, which teeth need to develop. When researchers studied mice lacking the Usag-1 gene, the animals grew supernumerary teeth—extra teeth beyond the normal set. In mice deficient in USAG-1, trace deciduous incisors that would normally vanish instead survived and erupted as excess teeth.

Researchers also used Runx2-deficient mice, which model congenital tooth agenesis in humans. Suppressing USAG-1 in these mice—either by deleting the gene or by silencing it with small interfering RNA (siRNA)—reversed the agenesis and allowed teeth to develop. Earlier work by Kiso and colleagues (Kiso et al., 2014) showed that the balance between USAG-1 and BMP-7 governs whether extra teeth form.

The takeaway was consistent: USAG-1 holds tooth growth in check, and removing its influence lets nature’s spare teeth come through.

How does anti-USAG-1 antibody therapy regenerate teeth?

Knowing that suppressing USAG-1 helps teeth grow was only half the answer. The next question was whether a drug could do the same thing safely—without disrupting BMP and Wnt everywhere else in the body.

A team from Kyoto University and the University of Fukui tackled this challenge. In a 2021 study published in Science Advances, Murashima-Suginami and colleagues tested several monoclonal antibodies designed to neutralize USAG-1 (Murashima-Suginami et al., 2021).

The results pointed to a clear winner. Because USAG-1 interacts with both BMP and Wnt, several antibodies caused poor birth and survival rates in mice—a sign they were interfering with whole-body development. But one antibody disrupted only the USAG-1–BMP interaction, leaving Wnt signaling intact. This antibody proved both effective and far safer.

The standout finding: a single administration of this antibody was enough to generate a whole new tooth in mice. The team then confirmed the same benefit in ferrets. Ferrets matter here because they are diphyodont animals with dental patterns much closer to humans than rodents are. Growing a whole tooth in a non-rodent model was a major step toward human relevance.

This research underpins the drug now being tested in people. A USAG-1-targeting treatment entered Phase I human trials in 2024, with safety first being assessed in healthy adults before the work moves toward children with congenital tooth agenesis.

What does the human teeth atlas tell us about dental stem cells?

Regrowing teeth is not only about switching genes on and off. It also depends on understanding the cells that build and maintain teeth—and that is where single-cell sequencing has been transformative.

Scientists at the University of Zurich mapped a complete single-cell atlas of human teeth, published in iScience. Using single-cell sequencing, they identified every cell type making up the dental pulp and the periodontium, the tissue surrounding and anchoring the tooth.

Two findings stand out for regenerative medicine:

1. Both tissues harbor mesenchymal stem cells (MSCs) with regenerative potential. Dental pulp stem cells and periodontal stem cells are promising raw material for rebuilding tooth tissue.
2. The microenvironment matters. Although pulp and periodontal MSCs are biologically similar, their surrounding environments drive major differences in how they behave. In other words, where a stem cell sits shapes what it can do.

This detailed cell map gives researchers a reference for guiding stem cells toward the right fate—a foundation for future cell-based therapies.

Why are antibody therapies more promising than tissue engineering?

For years, tooth regeneration research leaned on tissue engineering: combining cells, scaffolds, and growth factors to build a tooth in the lab and implant it. The approach is technically demanding, expensive, and difficult to scale.

Antibody-based therapy takes a different route. Instead of constructing a tooth from scratch, it prompts the body to grow its own using tooth germs that are already present. As Manabu Sugai, a co-author of the 2021 study, put it: “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.”

Choose antibody therapy if the goal is a simpler, cell-free treatment that works across many forms of congenital agenesis—it requires no lab-grown tissue and, in animal models, worked with a single dose. Tissue engineering may still matter for cases where no tooth germ exists to reactivate, such as some forms of adult tooth loss, though it remains far harder to deliver.

How will biomarkers and precision medicine shape tooth regeneration?

Not every case of missing teeth is the same. The genetics, severity, and underlying biology vary widely from person to person—so treatments will likely need to be tailored.

Next-generation sequencing now lets clinicians screen panels of agenesis-linked genes such as MSX1, PAX9, WNT10A, and EDA to pinpoint the cause of a patient’s missing teeth. Combined with advanced imaging, these tools can reveal whether dormant tooth germs are present and how a patient might respond to therapy.

This is the foundation of precision medicine in dentistry: matching the right regenerative treatment to the right patient based on their genetic and biological profile, rather than applying one approach to everyone.

The future of regrowing teeth

Tooth regeneration has shifted from a distant dream to an active clinical pursuit. The breakthrough came from a precise insight—that USAG-1 acts as a brake on tooth growth, and that a carefully designed antibody can release that brake without disturbing the rest of the body.

The research published by Ravi, Murashima-Suginami, Kiso, and colleagues ties these threads together: the genetics of agenesis, the dormant third dentition, animal models, the human teeth atlas, and the promise of precision medicine. With Phase I human trials now underway, the coming years should reveal whether what worked in mice and ferrets can work for people.

If you have missing teeth or a family history of tooth agenesis, talk to your dentist about genetic screening options and keep an eye on clinical trial developments. The era of regrowing teeth may be closer than you think.

Frequently asked questions

What is USAG-1 and why does it matter for tooth growth?

USAG-1 (Uterine Sensitization Associated Gene-1) is a protein that suppresses BMP signaling, which teeth need to develop. By limiting extra tooth germs, USAG-1 acts as a natural brake on tooth growth. Blocking it can release dormant teeth and allow them to develop.

Has tooth regeneration been tested in humans yet?

A drug targeting USAG-1 entered Phase I human trials in 2024. These trials first assess safety in healthy adults before moving toward children with congenital tooth agenesis. Results in humans are still pending.

Who could benefit most from anti-USAG-1 therapy?

People with congenital tooth agenesis—including hypodontia and oligodontia—are the primary focus, especially those who still have dormant tooth germs that the therapy can reactivate. Whether it can help adults who lost teeth to injury or disease is still being studied.

How is tooth regeneration different from dental implants?

Implants are artificial titanium posts that replace a missing tooth’s root and crown. Tooth regeneration aims to grow a real, living tooth from the body’s own tissue, restoring natural function rather than substituting it with a synthetic device.

Which genes are linked to missing teeth?

The genes most commonly associated with tooth agenesis include WNT10A, MSX1, PAX9, EDA, AXIN2, LTBP3, and TP63. WNT10A variants are the most frequent genetic cause of isolated hypodontia and oligodontia.