Can an Antibody Regrow Teeth? What the Anti-USAG-1 Study Showed and What It Did Not
What is new: in a paper published on 12 February 2021 in Science Advances, researchers from Kyoto University, Osaka University, the University of Fukui and the Aichi Human Service Center reported that a single injection of an antibody against a protein called USAG-1 caused mice to grow whole extra teeth, and rescued missing teeth in mice bred to lack them. A related antibody produced an extra front tooth in ferrets. Everything in that paper was done in animals. It is the reason "tooth regrowth drug" headlines exist, so it is worth reading what it actually measured.
This page walks through the study itself: the question, the experiments, the numbers the authors report, and the limits they state. It does not give dental advice, and nothing here is a treatment you can get.
Why we have a fixed number of teeth
Teeth form from small buds in the jaw. Whether a bud keeps growing depends on a set of chemical signals passed between two tissue layers. The paper names the main ones: bone morphogenetic protein (BMP), fibroblast growth factors, Sonic hedgehog and Wnt. These signals push development forward and are held in check by inhibitors.
USAG-1 (uterine sensitization-associated gene-1, also called SOSTDC1, ectodin or WISE) is one of those inhibitors. It works on two of the main signals at once: it binds BMP directly, and it binds LRP5/6, a co-receptor that Wnt needs. Mice that lack the USAG-1 gene grow extra teeth, which earlier work had already shown.
The number of teeth is normally tightly controlled, but the authors note that it is higher or lower than usual from birth in about 1% of people. Having fewer teeth than normal is called tooth agenesis; having more is called supernumerary teeth. The team's question was whether switching USAG-1 off could restore teeth that never formed.
What the researchers did
The study had three parts.
- Genetic crosses. They bred mice that lack USAG-1 with two strains that are missing teeth because of other genes (Msx1 and EDA1), then looked at the offspring's teeth.
- Antibodies. They made five mouse monoclonal antibodies against USAG-1, numbered #12, #16, #37, #48 and #57, and tested what each one blocked and what happened when it was given to animals.
- A second species. They gave the most promising BMP-blocking antibody to young ferrets, whose teeth are arranged more like ours than a mouse's are.
Part 1: removing the gene
Mice lacking both USAG-1 and Msx1 were rare: only 3 of 151 littermates had that combination, although about one in sixteen were expected. All three had normal third molars in the upper jaw, although tooth development is arrested early in Msx1-deficient mice. Their cleft palate, another feature of the Msx1 strain, was not corrected.
In the EDA1 strain, 75% of mice that still had USAG-1 were missing molars in the lower jaw. Mice lacking both genes instead had normal teeth, extra teeth or fused molars. The hair and tail features of the EDA1 strain stayed the same. In other words, removing USAG-1 changed the teeth and nothing else that the authors tracked.
Part 2: blocking the protein with antibodies
The five antibodies split into three groups depending on which job of USAG-1 they interfered with. The table summarises what the paper reports for each.
| Antibody | What it interfered with (lab tests) | Reported result in animals |
|---|---|---|
| #12 | USAG-1 binding to BMP | Extra teeth in mutant mice; low birth and survival rates |
| #16 | USAG-1 binding to Wnt co-receptor; low affinity | Rescued missing molars; extra teeth in mutant mice; low birth and survival rates |
| #37 | USAG-1 binding to BMP | Rescued missing molars at a high rate, dose-dependent; extra teeth; used in ferrets |
| #48 | USAG-1 binding to Wnt co-receptor; low affinity | Rescued missing molars; low birth and survival rates |
| #57 | Both BMP and Wnt (in screening); later found not to block LRP6 binding | Rescued missing molars; extra teeth even in normal (wild-type) mice, dose-dependent; fused upper molars instead of extra teeth there |
Source: Murashima-Suginami et al., Science Advances 7(7):eabf1798, figures 2, 3 and 5 as described in the text.
The antibodies were given once, systemically, to pregnant mice of the EDA1 strain, and the offspring's teeth were examined. The two antibodies that worked best, #37 and #57, both neutralised USAG-1's effect on BMP. The authors conclude that "a single systemic administration of a neutralizing antibody can generate a whole tooth" in mice.
The key result: it is BMP, not Wnt
Because USAG-1 acts on two signals, the team wanted to know which one mattered for tooth number. They mapped where antibody #37 binds and found it reacts with a ten-amino-acid stretch of USAG-1 (VNDKTRTQRI). That stretch sits far from the part of USAG-1 that docks onto LRP5/6, the Wnt co-receptor. Consistent with that, #37 did not change USAG-1's effect on Wnt.
In a separate binding test, antibody #16 almost completely stopped USAG-1 from binding the LRP6 fragment and #48 partly did, while #12, #37 and #57 did not. Put together, the authors conclude that blocking USAG-1's brake on BMP, rather than on Wnt, is what produced the large changes: missing teeth restored, or a whole new tooth formed.
The ferret experiment
Mice are a limited model for human teeth: they do not replace their teeth the way we do. Ferrets have both baby teeth and adult teeth, with a dental pattern the authors describe as similar to humans. When young ferrets were given antibody #37, an extra upper front tooth (incisor) formed behind the adult teeth, which the authors suggest may be a "third dentition", a third set of teeth beyond baby and adult teeth.
That result came with conditions. The ferrets needed about five times the concentration used in mice, three doses instead of one, and immunosuppression. The extra tooth looked like a normal adult incisor but appeared to have a shorter root. These details rarely appear in headlines, and they matter for judging how close the approach is to people.
How far along is it, really?
Based on the paper alone, the work is at the animal stage. The authors are explicit about what is still needed:
- More animal models first. They write that clinical use "will require further investigation in nonrodent models, such as suncuses, dogs, or pigs, in addition to ferrets."
- Not every kind of missing tooth. Removing USAG-1 restored molars in Msx1-deficient mice but not their cleft palate, and the authors say the antibody "did not cure all tooth agenesis cases". They suggest the first use would be people born without teeth because of specific gene mutations, with those mutations used to choose patients.
- Safety signals in mice. Three of the five antibodies (#12, #16, #48) were linked to low birth and survival rates when given to pregnant mice. The authors note that because some mice were not born or did not survive, a role for Wnt cannot be fully excluded.
- Cross-reaction. Antibody #57 showed weak binding to sclerostin (SOST), a related protein from the same family of BMP inhibitors. The authors raise this as a possible reason #57 produced extra teeth even in normal mice.
- Dose and conditions in ferrets. Higher dose, repeated dosing and immunosuppression were needed to see the effect.
What about human trials? News reports describe a first-in-human safety trial of an anti-USAG-1 antibody in Japan. The paper discussed here contains no human data. The authoritative record of any trial's design, participants, dates and results is its entry in the Japan Registry of Clinical Trials (jRCT), listed in the sources below; that registry, not a video or a headline, is where its current status should be checked.
Why this approach is different from lab-grown teeth
Most tooth-regeneration research tries to build a new tooth from cells or tissue engineering. The authors point out that none of those methods are clinically usable yet, because of cost and safety. Their argument is that people and mice already carry small, arrested tooth buds, so the task is not to create a tooth from scratch but to release a brake that stops an existing bud from growing. A drug-like antibody, rather than transplanted cells, would be simpler to make and give, if it proves safe.
Common questions
Does this mean adults will be able to regrow lost teeth?
The 2021 paper does not test that. It shows restored teeth in mice bred to be missing them, extra teeth in normal mice, and one extra incisor in young ferrets under specific conditions. Its authors point first to people born without certain teeth because of specific gene mutations.
Is the antibody available anywhere?
No. Nothing in the study is an approved treatment. Any product claiming to regrow teeth with this mechanism should be treated with caution.
Why did some mice not survive?
The paper reports low birth and survival rates for three of the five antibodies when given to pregnant mice but does not give a full explanation. The two antibodies that worked best for teeth were not among them.
Who did the research, and was it approved?
The paper lists authors from Kyoto University's Graduate School of Medicine and Institute for Frontier Life and Medical Sciences, Osaka University's Institute for Protein Research, the University of Fukui, and the Aichi Human Service Center. It states that the animal work was approved by the Animal Research Committee of Kyoto University and that each experiment was repeated at least three times.
What is USAG-1's job in the body?
In this context, it acts as a brake on two growth signals, BMP and Wnt, by binding BMP and the Wnt co-receptor LRP5/6. The study suggests its brake on BMP is what limits tooth number.
Sources and how to check
- Murashima-Suginami A, Kiso H, Tokita Y, Mihara E, Nambu Y, Uozumi R, Tabata Y, Bessho K, Takagi J, Sugai M, Takahashi K. "Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling." Science Advances 7(7): eabf1798, published 12 February 2021. DOI: 10.1126/sciadv.abf1798
- PubMed record: PMID 33579703 · Open-access full text: PMCID PMC7880588
- Bibliographic data checked against Crossref and the open-access full text on 22 October 2026. The article is published under a Creative Commons Attribution 4.0 licence (CC BY 4.0); quotations above are from it. No figures from the paper are reproduced on this page.
- Japan Registry of Clinical Trials (jRCT), for the current status of any human study: jrct.niph.go.jp