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[P3-2-08] LPAR signaling pathway modulates alveolar bone formation

〇Jae-Young Kim¹, Anna Kim¹, Yam Prasad Aryal¹, Elina Pokharel¹, Wern-Joo Sohn³, Hitoshi Yamamoto⁴, Il-Ho Jang⁵, Gabor J Tigyi⁶, Seo-Young An², Tae-Young Kim¹ (1. Dept Biochem, Kyungpook Natl Univ Sch Dent , 2. Dept Oral Maxillofac Radiol, Kyungpook Natl Univ Sch Dent, 3. Dept K-Beauty Business, Daegu Hanny Univ Coll Cosme Pharm, 4. Dept Histol Dev Biol, Tokyo Dent Coll, 5. Dept Oral Biochem Mol, Pusan Natl Univ Sch Dent, 6. Dept Physiol Mol, Univ Tennessee)

キーワード：Lysophosphatidic acid receptors、G-protein-coupled receptors、SMAD2/3

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMC35 (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-specific responses, with AMC35 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 ten days after tooth extraction, AMC35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, TGF-β1 and SMAD2/3. The increased expression and the localization of these proteins suggest that AMC35 elicits osteoblast differentiation through TGF-β1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-β1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMC35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.