Name: Shin-ichi Tanabe

Institution:Group de Recherche en Écologie Buccale    
Email: tanabes33238@aol.com

Project Title

Release of soluble RANKL from monocytes and gingival fibroblasts mediated by Porphyromonas gingivalis

Short Project Description

There is now a consensus that chronic periodontitis is initiated by several bacterial species, including Porphyromonas gingivalis, that behave in a cooperative or synergistic fashion to produce the infection. While bacteria are the primary factor in the aetiology of periodontitis, tissue destruction is also a consequence of the host response to the bacterial challenge. Bioactive molecules which are linked to the host cell membrane by anchor structures, can be released from the cell surface by a proteolytic cleavage process called shedding and involving host metalloproteinases. Shedding is a mechanism by which cells down-regulate (co)-receptors and convert membrane-anchored proteins into soluble effectors.

Receptor activator of NF-κ B ligand (RANKL) is a recently described cytokine that promotes osteoclast differentiation and activation. RANKL exerts its biological effects through binding to its receptor, the receptor activator of NF-κ B (RANK) on osteoclasts. Based on the high potential of P. gingivalis in mediating shedding/proteolysis processes, we propose the following hypothesis: P. gingivalis induces the cell surface expression and shedding of RANKL in monocytes and gingival fibroblasts and thus modulates bone destruction in periodontitis. In this project, human cells will be stimulated with either bacterial cells, lipopolysaccharide or cysteine proteinases of P. gingivalis. Soluble RANKL released in the conditioned medium will be quantified by an enzyme-linked immunosorbent assay (ELISA) while cell surface expression of RANKL will be evaluated by immunofluorescence (FACS). In addition, RANKL gene expression will be determined by RT-PCR. Stimulation of human cells will also be performed in the presence of different components (proteinase inhibitors, kinase inhibitors, etc) to investigate the mechanisms involved in RANKL cell surface expression and shedding. Results from the proposed studies will increase our knowledge on the etiopathogenesis of periodontitis and may also help to develop new strategies for the management of severe forms of periodontitis.

Academic Qualifications

University of Tokushima: Japan, Ph D: Master of Dentistry

Most Recent Publications

Actinobacillus actinomycetemcomitans lipopolysaccharide regulates matrix metalloproteinase, tissue inhibitors of matrix metalloproteinase, and plasminogen activator production by human gingival fibroblasts. J Cell Physiol. 212:189-194, 2007

Salivary immunoglobulin A directed to oral microbial GroEL in patients with periodontitis and their potential protective role. Oral Microbiol Immunol. 21: 289-295, 2006

Influence of smoking on osseointegrated implant failure: a meta-analysis. Clin Oral Implants Res. 17: 473-478, 2006