The role of NOD-like receptors in the modulation of osteoclastogenesis and bone resorption during experimental periodontitis

Abstract

The bacterial plaque has been identified as an etiological agent in the pathogenesis of periodontal disease (PD). The NOD-like receptors (NLRs) are cytoplasmic proteins that sense microbial byproducts released by invasive bacteria. There is no data in the literature describing the role of NLRs in the stimulation of inflammatory response and development of PD. Since periodontopathogenic bacteria are able to invade and colonize some periodontal tissue cells, we hypothesize that NLRs activation by bacterial products may play an important role in cronification of inflammatory process and aggravation of bone loss on adavanced periodontitis. The purpose of this study is to determine the role of NOD1 and NOD2 receptors in the recognition of invasive periodontopathogenic bacteria such as Porphyromonas gingivalis during experimental periodontitis. We intend to evaluate the role of those receptors modulating immune response and bone resorption in experimental periodontitis using wild type and NOD1, NOD2 and NOD1/2 knockout mice. The production of proinflamatory and osteoclastogenic mediators will be evaluated by ELISA, FACS and PCR. The bone resorption will be evaluated by means of micro CT. Moreover, we will investigate the role of NOD1 and NOD2 in the osteoclastogenesis in vitro using culture and co-cultures assay of preosteoclasts with osteoblasts stimulated with bacteria or NLRs specific ligands. The findings of the present study will give rise to a better understanding of the mechanisms underliyng osteoclastogenesis and bone resorption, as well as provide knowledge that can help to the development of new therapeutic target for PD treatment. (AU)