The Relationship between Mutations in Gene-Specific Domains of Salivary Fibronectin (cFn) and Dynamin-2 (Dynm-2) and the Development of Porphyromonas gingivalis-Initiated Periodontitis

Abstract

Periodontitis is a chronic inflammatory disease characterized by the destruction of the supporting structures of the teeth. Its high prevalence and negative effects on quality of life make it one of the current problems in dentistry. Porphyromonas gingivalis (P. gingivalis) is the predominant periodontal pathogen that expresses a number of virulence factors involved in the pathogenesis of periodontitis. P. gingivalis fimbriae are a critical factor in the interaction between the organism and the host tissue. They promote both bacterial adhesion and invasion into the target sites. Fimbriae are capable of binding to human saliva components, extracellular matrix proteins, and commensal bacteria, as well as firmly binding to the cellular integrin α5β1. After attachment to α5β1-integrin, P. gingivalis is captured by cellular pseudopodia, which makes invagination through an actin-mediated pathway possible. It has been proven that the invagination event also requires the participation of the host cell dynamin, actin fibers, microtubules and lipid rafts. Work has emerged investigating mutations in the proline-rich terminal domain (PRD) and their impact on disease development. Salivary antimicrobial peptides are early protective factors against microbial attack. Of great interest is fibronectin (FN) as the main competitor of P. gingivalis fimbriae. The FN can interact with cells in three different regions: the central cell-binding domain (CCBD), the COOH terminal heparin-binding domain (Hep2), and the type III connecting segment (IIICS), including the CS1 region (Yamada, 1991). CCBD is the major cell-adhesion domain of FN and contains an Arg–Gly–Asp (RGD) motif that is recognized by members of the cell adhesion receptor integrin family, including a5b1, which is the primary FN receptor in many cell types. The work focuses on identifying the relationship between the development of periodontitis and the presence of mutations in the adhesion domains of salivary proteins such as cellular fibronectin (cFN) and dynamin-2 (DYNM2).