Odontogenic Ameloblast-associated Protein (ODAM) Mediates Junctional Epithelium Attachment to Teeth via Integrin-ODAM-Rho Guanine Nucleotide Exchange Factor 5 (ARHGEF5)-RhoA Signaling

• Published in: The Journal of biological chemistry 2015-06, Vol.290 (23), p.14740-14753
• Main Authors: Lee, Hye-Kyung, Ji, Suk, Park, Su-Jin, Choung, Han-Wool, Choi, Youngnim, Lee, Hyo-Jung, Park, Shin-Young, Park, Joo-Cheol
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - analysis; Carrier Proteins - metabolism; Cell Biology; Cell Line; Epithelial Attachment - metabolism; Epithelial Attachment - pathology; Fibronectins - analysis; Fibronectins - metabolism; Humans; Integrins - analysis; Integrins - metabolism; Intracellular Signaling Peptides and Proteins; junctional epithelium; Laminin - analysis; Laminin - metabolism; Mice; ODAM; periodontitis; Periodontitis - metabolism; Periodontitis - pathology; Proteins - analysis; Proteins - metabolism; Rho Guanine Nucleotide Exchange Factors - analysis; Rho Guanine Nucleotide Exchange Factors - metabolism; Rho signaling; rhoA GTP-Binding Protein - analysis; rhoA GTP-Binding Protein - metabolism; Signal Transduction; tooth; Tooth - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.648022

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. Background: Adhesion of the junctional epithelium (JE) to the tooth surface is crucial for maintaining periodontal health. Results: JE adhesion to the tooth surface is regulated via fibronectin/laminin-integrin-ODAM-ARHGEF5-RhoA signaling. Conclusion: ODAM mediates JE attachment to healthy teeth. Significance: We investigate ODAM function during JE development and regeneration and its functional significance in the initiation and progression of periodontal disease.