Phytocystatins Csin-CPI-2 as a possible therapeutic candidate for treatment of periodontal disease and rheumatoid arthritis

Abstract

Recently, a number of studies have pointed to a potential relationship between rheumatoid arthritis (RA) and periodontal disease (PD) driven in part by the common features shared by both diseases. Both RA and PD present similarities in the inflammatory pathways, in the imbalance between pro- and anti-inflammatory cytokines, and are associated with bone destruction mediated by inflammatory cytokines and chemokines altering bone metabolism. Since both diseases share many common features is it highly relevant to investigate new treatment modalities to treat concomitant RA and PD. Despite several medications available for the treatment of RA, such as bisphosphonates, anti rheumatic drugs (DMARD) and antiinflammatory drugs (NSAIDS), almost all of them possess some deleterious effect that might lead to adverse outcomes. Therefore, the use of cystatins as a potentially new class of boneprotective drugs might be considered a possible effective therapeutic candidate to treat bone diseases. Thus, our aim is to investigate the effect of a new class of drugs derived from the sweet orange tree, the phytocystatins Csin-CPI-2 that express cystatins with the ability to inhibit cathepsins. We hypothesized that phytocystatins could have the ability to inhibit osteoclast-driven bone loss in an animal model with PD and RA. For this purpose, DAB/1J male mice with PD induced by ligatures incubated with live P. gingivalis and CIA-induced arthritis will be treated with a systemic treatment with Csin-CPI-2 injected daily during the entire experimental period. The severity of collagen arthritis and periodontitis will be scored clinically, radiological, histopathological, immunological (markers of inflammation and autoreactivity) and microbiological.