Exploring a novel therapeutic agent in periodontitis

Abstract

Recently, we have screened several natural compounds in an attempt to identify one that is capable of promoting bone formation, blocking bone resorption and reducing inflammation utilizing several in vitro assays. One type of natural product is remarkably promising in promoting osteogenesis while improving bone matrix quality and stability and forming bone in vivo. Others have reported that this compound, namely hesperidin, blocks osteoclastogenesis and reduces inflammation significantly in the presence of bacteria. Our hypothesis is that hesperidin will lead to prevention/arrest of periodontal disease as this compound promotes osteogenesis, blocks osteoclastogenesis and reduces inflammatory response. To test our hypothesis, we propose the following specific aims: Specific objective #1: To evaluate, in vitro, the action of the hesperidin on osteogenesis and osteoclastogenesis. The cells will be submitted to the doses of 1, 100 and 500 ¼M hesperidin in experiments that will evaluate the differentiation and function of osteoblasts (evaluating the expression of genes regulating bone metabolism, formation of mineralized nodules, organization and maturation of collagen), and osteoclastogenesis (evaluating the differentiation of osteoclasts by TRAP, osteoclast activity and reabsorption points). Specific objective #2: To evaluate, in vivo, the therapeutic action of hesperidin on experimental periodontitis in mice. A model of periodontal disease will be used by injecting bacteria around the maxillary molars in mice. After the experimental period of induction of the disease, the mice will be treated with 1¼M 100¼M or 500¼M hesperidin by oral gavage. The samples (jaws) will be collected for analysis of the bone volume, through computerized microtomography - ¼CT, and stereometric analysis of the gingival inflammatory process (H&E). (AU)