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Periodontitis and Rheumatoid Arthritis - Association, Dual Treatment and Resolution

Grant number: 16/09876-4
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): November 01, 2016
Effective date (End): October 31, 2017
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Joni Augusto Cirelli
Grantee:Rafael Scaf de Molon
Supervisor: Marije Ingrid Koenders
Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: Radboud University Nijmegen, Netherlands  
Associated to the scholarship:15/21697-5 - A potentially new class of bone-protective drugs, phytocystatin from sweet orange Csin-CPI-2, as possible therapeutic candidate for treatment of bone diseases., BP.PD


Rheumatoid arthritis (RA) and periodontitis (PD) are prevalent chronic conditions associated with significant morbidity. Both conditions are characterized by chronic inflammation and local tissue destruction. Evidence from our and other groups indicates that RA and PD not only often concur, but may also have a shared etiopathogenesis. The production of inflammatory and microbial particles during PD may enhance arthritogenic immune activation. Furthermore, PD may induce a break in immune tolerance in genetically predisposed individuals, resulting in production of the RA-defining anti-citrullinated peptide antibodies (ACPA) and elevated Th17 subset responses. It is clinically highly relevant to investigate whether RA disease activity can be diminished by oral treatment of PD. Thus, the aim of this study will be establish and validate a novel combined model for chronic, progressive arthritis and periodontitis, aimed at closely mimicking human RA and PD using the rice rat model, and chronic adjuvant arthritis. To gain further insight into the interconnection of the two disease models at the immunological level, ACPA levels will be determined, T lymphocytes from spleen, draining and non-draining lymph nodes will be isolated, their responsiveness to various antigens investigated, and T cell subsets analyzed by flowcytometry. Subsequently, this model will be validated with current anti-rheumatic drugs such as anti-TNF treatment. Our next objective is to test the feasibility and efficacy of a new dual treatment modality for PD and RA using biomaterials for sustained local delivery. For this purpose, PLGA microspheres will be used as carrier for the local release of resolvin E1 during PD. To prove our concept that arthritis can be suppressed by treatment of PD, rice rats with chronic PD and induced arthritis will be treated with a periodontal treatment delivery system containing RvE1. The severity of chronic arthritis and periodontitis will be scored clinically, radiological, histopathological, immunological (markers of inflammation and autoreactivity) and microbiological.

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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; 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, . (16/09876-4, 15/21697-5)
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, . (15/21697-5, 16/09876-4)
LEGUIZAMON, N. DA PONTE; DE MOLO, R. S.; COLETTO-NUNES, G.; NOGUEIRA, A. V. B.; ROCHA, V, S.; NEO-JUSTINO, D. M.; SOARES-COSTA, A.; CERRI, P. S.; LERNER, U. H.; SOUZA, P. P. C.; et al. hytocystatin CsinCPI-2 Reduces Osteoclastogenesis and Alveolar Bone Los. JOURNAL OF DENTAL RESEARCH, v. 101, n. 2, . (14/05283-3, 18/10727-9, 18/10728-5, 16/09876-4, 15/21697-5)

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