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Although SLC26A2-related chondrodysplasia also affects craniofacial and tooth development, its specific role in these processes remains unclear. In this study, we explored the pivotal roles of SLC26A2-mediated sulfate metabolism during tooth development. We found that Slc26a2 was predominantly expressed in dental tissues, including odontoblasts and ameloblasts. Slc26a2 knockout (Slc26a2-KO-\u0394exon2) mice exhibited distinct craniofacial abnormalities, such as a retrognathic upper jaw, small upper incisors and upper molar hypoplasia. These mice also showed flattened odontoblasts and loss of nuclear polarity in upper incisors and molars, with significant reductions in odontoblast differentiation markers Dspp and Dmp1. Ex vivo and in vitro studies further revealed dentin matrix hypoplasia, tooth root shortening and downregulation of Wnt signaling in Slc26a2-deficient cells. These findings highlight the crucial role of SLC26A2-mediated sulfate metabolism in tooth development and offer insights into the mechanisms underlying dental abnormalities in patients with SLC26A2-related chondrodysplasias.<\/jats:p>","DOI":"10.1242\/dmm.052107","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T15:41:14Z","timestamp":1730994074000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>Slc26a2<\/i>-mediated sulfate metabolism is important in tooth development"],"prefix":"10.1242","volume":"17","author":[{"given":"Yuka","family":"Yoshida","sequence":"first","affiliation":[{"name":"Osaka University Graduate School of Dentistry 1 Department of Orthodontics and Dentofacial Orthopedics , , Osaka 565-0871 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