Specific gene variants influence dental symptoms in rare bone condition

In hypophosphatasia, a rare inherited condition that weakens bones and teeth, early tooth loss can be the first, or even the only obvious sign. Yet why dental symptoms differ so much between patients has remained unclear. Researchers at the University of Osaka have developed new mouse models that reproduce genetic changes seen in patients, revealing that teeth and their supporting tissues can be affected even when changes in the rest of the skeleton are mild.

The team introduced three variants of the ALPL gene found in patients and closely analyzed two models representing milder forms of the disease. Both showed reduced density of the bone surrounding the teeth and weaker tissues that anchor teeth in place. One model, carrying the p.R184W variant, showed little obvious skeletal change elsewhere but abnormalities in dentin, cementum, and tooth-supporting tissues. The other, carrying c.1559delT and p.F327L, showed mild skeletal changes together with broader dental defects, including reduced mineralization of enamel and dentin and thinner dentin.

Importantly, the differences in dental symptoms could not be explained by blood levels of tissue-nonspecific alkaline phosphatase (TNAP) alone. TNAP is an enzyme needed for proper hardening of bones and teeth. The findings indicate that the specific ALPL variant itself also influences how oral symptoms develop.

Some patients are diagnosed only after their baby teeth fall out early, even though they show almost no bone symptoms. We hope these models will help us develop dental treatments tailored to each patient's symptoms."

Rena Okawa, Associate Professor, University of Osaka 

The models could provide a platform for studying ways to prevent tooth loss, protect the jawbone around teeth, and improve the safety of dental treatments such as orthodontics. Because dental symptoms can appear before obvious skeletal problems, the work also highlights the potential role of dentists in earlier recognition of the disease.