Mechanisms involved in the regulation of 5-lipoxygenase pathway in experimentally-induced apical periodontitis

• Grant number: 10/17611-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: July 01, 2011
• End date: June 30, 2015
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Francisco Wanderley Garcia de Paula e Silva
• Grantee: Francisco Wanderley Garcia de Paula e Silva
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 14/14015-2 - Study of cell differentiation of the hematopoietic lineage via 5-lipoxygenase, BP.IC; 13/09595-7 - The role of selective and non-selective inhibitors enzyme cyclooxygenase-2 and 5-lipoxygenase enzyme in osteoclastogenesis after the development of experimental periapical, BP.IC; 12/08421-2 - Investigation of the role of cyclooxygenase-2 in periapical bone resorption induced by bacterial lipopolysaccharide, BP.DR

Abstract

Apical periodontitis represents a localized immune-inflammatory response directed against microorganisms inside the root canal. Previously we have demonstrated a poor bone healing following root canal treatment, indicating that improper root canal therapy has been used probably due to the low understanding of the dynamics of the pathology. Therefore, the investigation of the biological mediators involved in the development and progression of apical periodontitis grows in importance in order to determinate potencial therapeutic targets. Considering that leukotrienes, produced from arachidonic acid metabolism, are important mediators of the inflammatory response and that no report of the role of this mediator in inflammatory apical periodontitis has been found, the purpose of this study will be the evaluation of the 5-lipoxygenase (5-LO) pathway involvement in the development of experimentally-induced apical periodontitis in C57BL/6 and 5-LO knockout (5-LO-/-; 129-Alox5tm1Fun) mice. In addition, the mechanisms involved in the synthesis of leukotrienes in periodontal ligament cells will be investigated aiming to detect different levels of leukotriene regulation which could be used as alternative routes to pharmacological inhibition. The tissue and cells obtained from mice will be immunolabed for proteins and enzymes involved in the synthesis and convertion of leukotrienes. cDNA microarrays will be used to reveal novel genes involved in the activation of the 5-LO pathway. The activity of tartrate resistant acid phosphatase (TRAP) will be evaluated to detect the presence and activity of osteoclasts in the tissues. Statistical analysis will be performed according to data distribution (± = 0.05). (AU)

Scientific publications

(21)

(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)

DA SILVA, LEA ASSED BEZERRA; LONGO, DANIELE LUCCA; STUANI, MARIA BERNADETE SASSO; DE QUEIROZ, ALEXANDRA MUSSOLINO; DA SILVA, RAQUEL ASSED BEZERRA; NELSON-FILHO, PAULO; VIEIRA, HELOISA APARECIDA ORSINI; PUCINELLI, CAROLINA MASCHIETTO; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. Effect of root surface treatment with denusomab after delayed tooth replantation. CLINICAL ORAL INVESTIGATIONS, v. 25, n. 3, JUL 2020. (10/17611-4)

RIBEIRO-SANTOS, FERNANDA REGINA; ARNEZ, MAYA FERNANDA MANFRIN; DE CARVALHO, MARCIO SANTOS; DA SILVA, RAQUEL ASSED BEZERRA; POLITI, MARILIA PACIFICO LUCISANO; DE QUEIROZ, ALEXANDRA MUSSOLINO; NELSON-FILHO, PAULO; DA SILVA, LEA ASSED BEZERRA; FACCIOLI, LUCIA HELENA; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. Effect of non-steroidal anti-inflammatory drugs on pulpal and periapical inflammation induced by lipopolysaccharide. CLINICAL ORAL INVESTIGATIONS, v. 25, n. 11, p. 6201-6209, NOV 2021. (12/08421-2, 10/17611-4)

GONCALVES, JULIANA DE LIMA; ALVES DUARTE, ANA CAROLINE; ALMEIDA-JUNIOR, LUCIANO APARECIDO; DE CARVALHO, FABRICIO KITAZONO; DE QUEIROZ, ALEXANDRA MUSSOLINO; MANFRIN ARNEZ, MAYA FERNANDA; FACCIOLI, LUCIA HELENA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY. Enamel biomineralization under the effects of indomethacin and celecoxib non-steroidal anti-inflammatory drugs. SCIENTIFIC REPORTS, v. 12, n. 1, p. 13-pg., 2022-09-22. (14/07125-6, 10/17611-4, 21/09272-0)

QUEIROZ, ALEXANDRA M.; CARPIO-BONILLA, CLAUDIA M.; ARNEZ, MAYA F. M.; DOS SANTOS, THAIS T.; PALMA-DIBB, REGINA G.; OLIVEIRA, HARLEY F.; NELSON-FILHO, PAULO; SILVA, LEA A. B.; PAULA-SILVA, FRANCISCO W. G.. Radiotherapy Activates Matrix Metalloproteinases in the Dentinoenamel Junction of Primary Teeth. JOURNAL OF DENTISTRY FOR CHILDREN, v. 87, n. 2, p. 83-89, MAY 2020. (16/16243-8, 10/17611-4)

LAURA ALVES BASTOS; FRANCINE LORENCETTI SILVA; JOÃO PEDRO DE QUEIROZ THOMÉ; MAYA FERNANDA MANFRIN ARNEZ; LÚCIA HELENA FACCIOLI; FRANCISCO WANDERLEY GARCIA PAULA-SILVA. Effects of Papain-Based Gel Used For Caries Removal on Macrophages and Dental Pulp Cells. Brazilian Dental Journal, v. 30, n. 5, p. 484-490, 2019-10-07. (14/14015-2, 10/17611-4)

DA SILVA, FRANCINE LORENCETTI; DE CAMPOS CHAVES LAMARQUE, GIULIANA; DE OLIVEIRA, FERNANDA MARIA MACHADO PEREIRA CABRAL; NELSON-FILHO, PAULO; DA SILVA, LEA ASSED BEZERRA; SEGATO, RAQUEL ASSED BEZERRA; FACCIOLI, LUCIA HELENA; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. eukotriene B-4 loaded in microspheres regulate the expression of genes related to odontoblastic differentiation and biomineralization by dental pulp stem cell. BMC ORAL HEALTH, v. 22, n. 1, FEB 23 2022. (10/17611-4)

RIBEIRO-SANTOS, FERNANDA REGINA; ARNEZ, MAYA FERNANDA MANFRIN; DE CARVALHO, MARCIO SANTOS; DA SILVA, RAQUEL ASSED BEZERRA; POLITI, MARILIA PACIFICO LUCISANO; DE QUEIROZ, ALEXANDRA MUSSOLINO; NELSON-FILHO, PAULO; DA SILVA, LEA ASSED BEZERRA; FACCIOLI, LUCIA HELENA; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. Effect of non-steroidal anti-inflammatory drugs on pulpal and periapical inflammation induced by lipopolysaccharide. CLINICAL ORAL INVESTIGATIONS, APR 2021. (12/08421-2, 10/17611-4)

FRANCISCO WANDERLEY GARCIA PAULA-SILVA; FERNANDA REGINA RIBEIRO-SANTOS; IGOR BASSI FERREIRA PETEAN; MAYA FERNANDA MANFRIN ARNEZ; LUCIANO APARECIDO DE ALMEIDA-JUNIOR; FABRÍCIO KITAZONO DE CARVALHO; LÉA ASSED BEZERRA DA SILVA; LÚCIA HELENA FACCIOLI. Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis. Journal of Applied Oral Science, v. 28, 2020-05-11. (10/17611-4)

QUEIROZ, ALEXANDRA MUSSOLINO; CARPIO BONILLA, CLAUDIA MARIA; PALMA-DIBB, REGINA GUENKA; OLIVEIRA, HARLEY FRANCISCO; NELSON-FILHO, PAULO; BEZERRA SILVA, LEA ASSED; PACIFICO LUCISANO, MARILIA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY. Radiotherapy Activates and Protease Inhibitors Inactivate Matrix Metalloproteinases in the Dentinoenamel Junction of Permanent Teeth. Caries Research, v. 53, n. 3, p. 253-259, 2019. (10/17611-4)

FRANCINE LORENCETTI-SILVA; PRISCILLA APARECIDA TARTARI PEREIRA; ALYNE FÁVERO GALVÃO MEIRELLES; LÚCIA HELENA FACCIOLI; FRANCISCO WANDERLEY GARCIA PAULA-SILVA. Prostaglandin E2 Induces Expression of Mineralization Genes by Undifferentiated Dental Pulp Cells. Brazilian Dental Journal, v. 30, n. 3, p. 201-207, 2019-06-03. (10/17611-4)

LONGO, DANIELE LUCCA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; FACCIOLI, LUCIA HELENA; GATON-HERNANDEZ, PATRICIA MARIA; DE QUEIROZ, ALEXANDRA MUSSOLINO; BEZERRA DA SILVA, LEA ASSED. Cytotoxicity and cytokine expression induced by silorane and methacrylate-based composite resins. Journal of Applied Oral Science, v. 24, n. 4, p. 338-343, JUL-AUG 2016. (10/17611-4)

GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; FERREIRA PETEAN, IGOR BASSI; BEZERRA DA SILVA, LEA ASSED; FACCIOLI, LUCIA HELENA. Dual Role of 5-Lipoxygenase in Osteoclastogenesis in Bacterial-induced Apical Periodontitis. JOURNAL OF ENDODONTICS, v. 42, n. 3, p. 447-454, MAR 2016. (10/17611-4)

DALTOE, MARIANA O.; PAULA-SILVA, FRANCISCO WANDERLEY G.; FACCIOLI, LUCIA H.; GATON-HERNANDEZ, PATRICIA M.; DE ROSSI, ANDIARA; BEZERRA SILVA, LEA ASSED. Expression of Mineralization Markers during Pulp Response to Biodentine and Mineral Trioxide Aggregate. JOURNAL OF ENDODONTICS, v. 42, n. 4, p. 596-603, APR 2016. (14/25692-5, 10/17611-4)

RIBEIRO-SANTOS, FERNANDA REGINA; DA SILVA, GEYSON GALO; FERREIRA PETEAN, IGOR BASSI; MANFRIN ARNEZ, MAYA FERNANDA; BEZERRA DA SILVA, LEA ASSED; FACCIOLI, LUCIA HELENA; GARCIA PAULA-SILVA, FRANCISCO WANDERLEY. Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage. Journal of Applied Oral Science, v. 27, 2019. (13/09595-7, 10/17611-4)

GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; RIBEIRO-SANTOS, FERNANDA REGINA; FERREIRA PETEAN, IGOR BASSI; MANFRIN ARNEZ, MAYA FERNANDA; DE ALMEIDA-JUNIOR, LUCIANO APARECIDO; DE CARVALHO, FABRICIO KITAZONO; BEZERRA DA SILVA, LEA ASSED; FACCIOLI, LUCIA HELENA. Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E-2 and leukotriene B-4 signaling in apical periodontitis. Journal of Applied Oral Science, v. 28, 2020. (10/17611-4)

PETEAN, I. B. F.; ALMEIDA-JUNIOR, L. A.; ARNEZ, M. F. M.; QUEIROZ, A. M.; SILVA, R. A. B.; SILVA, L. A. B.; FACCIOLI, L. H.; PAULA-SILVA, F. W. G.. Celecoxib treatment dampens LPS-induced periapical bone resorption in a mouse model. International Endodontic Journal, v. 54, n. 8, p. 1289-1299, AUG 2021. (10/17611-4, 13/09595-7)

TAIRA, THAISE MAYUMI; RIBEIRO, VITOR LUIS; SILVA RIBEIRO, YURI JIVAGO; BEZERRA DA SILVA, RAQUEL ASSED; BEZERRA DA SILVA, LEA ASSED; LUCISANO POLITI, MARILIA PACIFICO; FACCIOLI, LUCIA HELENA; GARCIA PAULA-SILVAA, FRANCISCO WANDERLEY. Gene expression data of inflammatory mediators in apical periodontitis in 129 (wild type) and 5-lipoxygenase knockout mice. DATA IN BRIEF, v. 40, p. 8-pg., 2022-02-01. (19/00204-1, 10/17611-4)

IGOR BASSI FERREIRA PETEAN; ALICE CORRÊA SILVA-SOUSA; TAMARA JUSTINIANO CRONENBOLD; JARDEL FRANCISCO MAZZI-CHAVES; LEA ASSED BEZERRA DA SILVA; RAQUEL ASSED BEZERRA SEGATO; GUILHERME ASSED PIEDADE DE CASTRO; ERIKA CALVANO KUCHLER; FRANCISCO WANDERLEY GARCIA PAULA-SILVA; MANOEL DAMIÃO SOUSA-NETO. Genetic, Cellular and Molecular Aspects involved in Apical Periodontitis. Brazilian Dental Journal, v. 33, n. 4, p. 1-11, 2022-08-26. (13/09595-7, 15/06866-5, 10/17611-4)

PETEAN, IGOR BASSI FERREIRA; SILVA-SOUSA, ALICE CORREA; DA SILVA, RAQUEL ASSED BEZERRA; LUCISANO, MARILIA PACIFICO; DA SILVA, LEA ASSED BEZERRA; DE CASTRO, GUILHERME PIEDADE ASSED; SOUSA-NETO, MANOEL DAMIAO; FACCIOLI, LUCIA HELENA; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. Systemic inhibition of 5-lipoxygenase by MK-886 exacerbates apical periodontitis bone loss in a mouse model. BMC ORAL HEALTH, v. 23, n. 1, p. 9-pg., 2023-01-10. (14/07125-6, 10/17611-4, 13/09595-7)

DE QUEIROZ, ALEXANDRA MUSSOLINO; BONILLA, CLAUDIA MARIA CARPIO; FURTADO, TAISSA CASSIA DE SOUZA; PALMA-DIBB, REGINA GUENKA; OLIVEIRA, HARLEY FRANCISCO DE; ARNEZ, MAYA FERNANDA MANFRIN; CARVALHO, FABRICIO KITAZONO DE; PAULA-SILVA, FRANCISCO WANDERLEY GARCIA. Acid challenge exacerbates activation of matrix metalloproteinases in permanent teeth undergoing radiotherapy. BRAZILIAN ORAL RESEARCH, v. 38, p. 9-pg., 2024-01-01. (21/08558-7, 10/17611-4)

GARCIA PAULA-SILVA, FRANCISCO WANDERLEY; MANFRIN ARNEZ, MAYA FERNANDA; FERREIRA PETEAN, IGOR BASSI; ALMEIDA-JUNIOR, LUCIANO APARECIDO; BEZERRA DA SILVA, RAQUEL ASSED; BEZERRA DA SILVA, LEA ASSED; FACCIOLI, LUCIA HELENA. Effects of 5-lipoxygenase gene disruption on inflammation, osteoclastogenesis and bone resorption in polymicrobial apical periodontitis. ARCHIVES OF ORAL BIOLOGY, v. 112, APR 2020. (10/17611-4)