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A potentially new class of bone-protective drugs, phytocystatin from sweet orange Csin-CPI-2, as possible therapeutic candidate for treatment of bone diseases

Grant number: 15/21697-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2016
Effective date (End): April 01, 2020
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Joni Augusto Cirelli
Grantee:Rafael Scaf de Molon
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):16/09876-4 - Periodontitis and rheumatoid arthritis - association, dual treatment and resolution, BE.EP.PD


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 anti-inflammatory 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 bone-protective 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.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE MOLON, RAFAEL SCAF; THURLINGS, ROGIER M.; WALGREEN, BIRGITTE; HELSEN, MONIQUE M.; VAN DER KRAAN, PETER M.; CIRELLI, JONI AUGUSTO; KOENDERS, I, MARIJE. Systemic Resolvin E1 (RvE1) Treatment Does Not Ameliorate the Severity of Collagen-Induced Arthritis (CIA) in Mice: A Randomized, Prospective, and Controlled Proof of Concept Study. Mediators of Inflammation, v. 2019, OCT 31 2019. Web of Science Citations: 0.
DE MOLON, RAFAEL SCAF; ROSSA, JR., CARLOS; THURLINGS, ROGIER M.; CIRELLI, JONI AUGUSTO; KOENDERS, MARIJE I. Linkage of Periodontitis and Rheumatoid Arthritis: Current Evidence and Potential Biological Interactions. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 18 SEP 2 2019. Web of Science Citations: 1.

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