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 Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): April 01, 2016
• Effective date (End): June 01, 2020
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Joni Augusto Cirelli
• Grantee: Rafael Scaf de Molon
• Host 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

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 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

(8)

(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)

JOÃO ANTONIO CHAVES DE SOUZA; FERNANDO AUGUSTO CINTRA MAGALHÃES; GUILHERME JOSE PIMENTEL LOPES DE OLIVEIRA; RAFAEL SCAF DE MOLON; JOSÉ ANTONIO ZUANON; PEDRO PAULO CHAVES DE SOUZA. Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice. Brazilian Oral Research, v. 34, 2020-02-10. (15/21697-5, 14/05283-3)

KIM, YEON JUNG; DE MOLON, RAFAEL SCAF; DA SILVA, VANESSA CAMILA; VEIGA CONRADO, MARINA CAVALCANTI ALBUQUERQUE; SPOLIDORIO, LUIS CARLOS; ANTUNES ROQUE-BARREIRA, MARIA CRISTINA; CIRELLI, JONI AUGUSTO. Topical application of lectin Artin M improves wound healing in defects created in the palatal mucosa: an in vivo study in dogs. ODONTOLOGY, FEB 2020. (15/21697-5, 06/60642-2, 09/16432-1)

DE MOLON, RAFAEL SCAF; FIORI, LESLIE CRISTINE; ARRUDA VERZOLA, MARIO HENRIQUE; BELLUCI, MARINA MONTOSA; DE SOUZA FALONI, ANA PAULA; RODRIGUES PEREIRA, ROSA MARIA; TETRADIS, SOTIRIOS; PEREZ ORRICO, SILVANA REGINA. Long-term evaluation of alendronate treatment on the healing of calvaria bone defects in rats. Biochemical, histological and immunohistochemical analyses. ARCHIVES OF ORAL BIOLOGY, v. 117, SEP 2020. (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, OCT 31 2019. (15/21697-5, 16/09876-4)

DA SILVA, VANESSA CAMILA; DE MOLON, RAFAEL SCAF; MARTINS, RENATO PARSEKIAN; RIBEIRO, FERNANDO SALIMON; FARIAS PONTES, ANA EMILIA; ZANDIM-BARCELOS, DANIELA LEAL; MANZOLLI LEITE, FABIO RENATO; BENATTI NETO, CARLOS; CHIERICI MARCANTONIO, ROSEMARY ADRIANA; CIRELLI, JONI AUGUSTO. Effects of orthodontic tooth extrusion produced by different techniques, on the periodontal tissues: a histological study in dogs. ARCHIVES OF ORAL BIOLOGY, v. 116, AUG 2020. (15/21697-5)

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. (16/09876-4, 15/21697-5)

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, JUL 2021. (18/10728-5, 16/09876-4, 18/10727-9, 15/21697-5, 14/05283-3)

BELLUCI, MARINA MONTOSA; DE MOLON, RAFAEL SCAF; ROSSA, JR., CARLOS; TETRADIS, SOTIRIOS; GIRO, GABRIELA; CERRI, PAULO SERGIO; MARCANTONIO, JR., ELCIO; PERES ORRICO, SILVANA REGINA. Severe magnesium deficiency compromises systemic bone mineral density and aggravates inflammatory bone resorption. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 77, MAR 2020. (08/04855-2, 15/21697-5)