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To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG\u201035 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type\u2010specific responses, with AMG\u201035 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG\u201035 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF\u2010\u03b21) and SMAD2\/3. The increased expression and the localization of these proteins suggest that AMG\u201035 elicits osteoblast differentiation through TGF\u2010\u03b21 and SMAD2\/3 signaling. These results indicate that LPAR2\/TGF\u2010\u03b21\/SMAD2\/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG\u201035 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.<\/jats:p>","DOI":"10.1002\/jcp.31148","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T12:55:26Z","timestamp":1703681726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional modulation of lysophosphatidic acid type 2 G\u2010protein coupled receptor facilitates alveolar bone formation"],"prefix":"10.1002","volume":"239","author":[{"given":"Tae\u2010Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Dentistry, IHBR, Kyungpook National University Daegu South 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