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Hypophosphatasia (HPP) is an inherited error in metabolism resulting from loss-of-function variants in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP plays a crucial role in biomineralization of bones and teeth, in part by reducing levels of inorganic pyrophosphate (PPi), an inhibitor of biomineralization. HPP onset in childhood contributes to rickets, including growth plate defects and impaired growth. In adulthood, osteomalacia from HPP contributes to increased fracture risk. HPP also affects oral health. The dentoalveolar complex, that is, the tooth and supporting connective tissues of the surrounding periodontia, include 4 unique hard tissues: enamel, dentin, cementum, and alveolar bone, and all can be affected by HPP. Premature tooth loss of fully rooted teeth is pathognomonic for HPP. Patients with HPP often have complex oral health issues that require multidisciplinary dental care, potentially involving general or pediatric dentists, periodontists, prosthodontists, and orthodontists. The scientific literature to date has relatively few reports on dental care of individuals with HPP. Animal models to study HPP included global Alpl knockout mice, Alpl mutation knock-in mice, and mice with tissue-specific conditional Alpl ablation, allowing for new studies on pathological mechanisms and treatment effects in dental and skeletal tissues. Enzyme replacement therapy (ERT) in the form of injected, recombinant mineralized tissue-targeted TNAP has been available for nearly a decade and changed the prognosis for those with HPP. However, effects of ERT on dental tissues remain poorly defined and limitations of the current ERT have prompted exploration of gene therapy approaches to treat HPP. Preclinical gene therapy studies are promising and may contribute to improved oral health in HPP. [ABSTRACT FROM AUTHOR]

Resveratrol (RV-3, 5, 4'-trihydroxystilbene) is a natural compound found in plants like red grapes, berries, and peanuts, with promising effects on dental health. It helps strengthen tooth enamel by promoting remineralization, making the teeth more resistant to decay caused by acid-producing bacteria. RV also shields dentin, a vulnerable layer beneath the enamel, from erosion and sensitivity. Its anti-inflammatory properties can reduce inflammation associated with dental conditions such as pulpitis and endodontic diseases. Moreover, RV's antimicrobial activity inhibits the growth of bacteria involved in dental plaque and biofilm formation, preventing their accumulation on the tooth surface. This contributes to a healthier oral environment and prolongs the lifespan of dental restorative materials. However, the research on RV's impact on dental health is in its early stages, and further studies are needed to confirm potential benefits. Important factors such as determining the optimal dosage, understanding its bioavailability, and assessing potential side effects require further investigation. This review focuses on the important role of RV in promoting dental health. It delves into various aspects, including its impact on root health, maintenance of the dental pulp, care for tooth enamel, effectiveness of dental restorative materials, and health of dentin., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

α-Smooth muscle actin (α-SMA) is an actin isoform commonly found within vascular smooth muscle cells. Moreover, α-SMA-positive cells are localized in the dental follicle (DF). DF is derived from alveolar bone (AB), cementum, and periodontal ligament (PDL). Therefore, α-SMA-positive cells in the periodontal tissue are speculated to be a marker for mesenchymal stem cells during tooth development. In particular, the mechanism of osteoblast differentiation is not clear. This study demonstrated the fate of α-SMA-positive cells around the tooth germ immunohistochemically. First, α-SMA- and Runx2-positive localization at embryonic days (E) 13, E14, postnatal days (P) 9, and P15 was demonstrated. α-SMA- and Runx2-positive cells were detected in the upper part of the DF at P1. At P9 and P15, α-SMA-positive cells in the PDL were detected in the upper and lower parts. The positive reaction of Runx2 was also localized in the PDL. Then, the distribution of α-SMA-positive cell progeny at P9 and P15 were clarified using α-SMA-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (α-SMA/tomato) mice. It has known that Runx2-positive cells differentiate into osteoblasts. In this study, some Runx2 and α-SMA-positive cells were localized in the DF and PDL. The lineage-tracing analysis demonstrated that the α-SMA/tomato-positive cells expressing Runx2 or Osterix were detected on the AB surface at P15. α-SMA/tomato-positive cells expressing type I collagen were found in the AB matrix. These results indicate that the progeny of the α-SMA-positive cells in the DF could differentiate into osteogenic cells. In conclusion, α-SMA could be a potential marker of progenitor cells that differentiate into osteoblasts., Competing Interests: Declarations. Ethics approval: All experiments were approved by the Animal Ethics Committee of the Health Sciences University of Hokkaido (Approval no. 23–031) and conducted according to the institutional guidelines and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)