title: Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling.
abstract: Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Although odontogenic ameloblast-associated protein (ODAM) is expressed in the JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in the normal JE of healthy teeth but absent in the pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from the JE following onset with JE attachment loss and detected in gingival crevicular fluid. ODAM induced RhoA activity and the expression of downstream factors, including ROCK (Rho-associated kinase), by interacting with Rho guanine nucleotide exchange factor 5 (ARHGEF5). ODAM-mediated RhoA signaling resulted in actin filament rearrangement. Reduced ODAM and RhoA expression in integrin β3- and β6-knockout mice revealed that cytoskeleton reorganization in the JE occurred via integrin-ODAM-ARHGEF5-RhoA signaling. Fibronectin and laminin activated RhoA signaling via the integrin-ODAM pathway. Finally, ODAM was re-expressed with RhoA in regenerating JE after gingivectomy in vivo. These results suggest that ODAM expression in the JE reflects a healthy periodontium and that JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. We also propose that ODAM could be used as a biomarker of periodontitis and peri-implantitis.
authors.affiliation: From the Departments of Oral Histology/Developmental Biology and.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: the Department of Periodontology, Anam Hospital, Korea University, 73 Inchonro, Anam-dong, Seongbuk-gu, Seoul 136-713, Korea, and.
authors.forename: Suk
authors.initials: S
authors.lastname: Ji
authors.affiliation: From the Departments of Oral Histology/Developmental Biology and.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: From the Departments of Oral Histology/Developmental Biology and.
authors.forename: Han-Wool
authors.initials: HW
authors.lastname: Choung
authors.affiliation: Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehagro, Chongro-gu, Seoul 110-744, Korea.
authors.forename: Youngnim
authors.initials: Y
authors.lastname: Choi
authors.affiliation: the Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, 173-82 Gumiro, Seongnam-si, Gyeonggi-do 463-707, Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: the Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital, 173-82 Gumiro, Seongnam-si, Gyeonggi-do 463-707, Korea.
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: From the Departments of Oral Histology/Developmental Biology and jcapark@snu.ac.kr.
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
mesh_terms: D000682:Amyloid; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D004846:Epithelial Attachment / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000032:analysis / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D014070:Tooth / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000378:metabolism*
chemical_list: C577229:ARHGEF5 protein, mouse; D000682:Amyloid; D002352:Carrier Proteins; D005353:Fibronectins; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D009363:Neoplasm Proteins; C480049:ODAM protein, human; C555400:ODAM protein, mouse; D011506:Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein
keywords: ODAM; Rho signaling; junctional epithelium; periodontitis; tooth