Odontogenic ameloblast-associated protein (ODAM) Mediates Junctional Epithelium Attachment to Tooth via Integrin-ODAM-Rho guanine nucleotide exchange factor 5 (ARHGEF5)-Ras homolog gene family member A (RhoA) Signaling [Signal Transduction]

April 24th, 2015 by Lee, H.-K., Ji, S., Park, S.-J., Choung, H.-W., Choi, Y., Lee, H.-J., Park, S.-Y., Park, J.-C.

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 JE, its molecular functions remain unknown. We investigated ODAM function during JE development and regeneration, as well as its functional significance in the initiation and progression of periodontitis and peri-implantitis. ODAM was expressed in normal JE of healthy tooth but was absent in pathologic pocket epithelium of diseased periodontium. In periodontitis and peri-implantitis, ODAM was extruded from 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, 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 beta 3- and 6-knockout mice revealed cytoskeleton reorganization in 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 JE reflects 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.
  • Posted in Journal of Biological Chemistry, Publications
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