Evaluation of periapical lesions induced in female osteoporotic rats subjected or not to treatment with bisphosphonate or cathepsin K inhibitor

• Grant number: 14/13238-8
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2014
• End date: November 30, 2016
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Paulo Nelson Filho
• Grantee: Paulo Nelson Filho
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Léa Assed Bezerra da Silva ; Raquel Assed Bezerra da Silva

Abstract

The aim of this study will be to evaluate periapical lesions induced in female osteoporotic rats subjected or not to treatment with bisphosphonate (alendronate - ALD) or cathepsin K inhibitor (odanacatib - ODN). Fifty animals will be randomly assigned to 6 groups: I - Sham surgery; II - Sham and periapical lesion; III - ovariectomy (OVX) and periapical lesion; IV - OVX, periapical lesion and ALD; V - OVX, periapical lesion and ODN; Group VI - OVX, periapical lesion and distilled water. Four weeks after OVX or sham surgery, groups IV, V and VI animals will start receiving medication or distilled water and the mandibular first molars of the rats in groups II, III, IV, V and VI will be subjected to induction of periapical lesion formation. Twenty-one days later, microbiological root canal sampling will be performed for quantification of microorganisms and the animals will be euthanized. Mineral bone density of the tibias of all animals will be evaluated. The left hemi-mandibles will be subjected to histotechnical processing and the hematoxylin and eosin-stained histological sections will be examined under conventional optical microscopy. Additionally, it will be performed morphometric analysis of periapical lesion size, tartrate-resistant acid phosphatase (TRAP) histoenzymology for identification of osteoclasts, Brown and Brenn staining for identification and localization of bacteria, and immunohistochemical analysis of osteoclastogenesis and cathepsin K markers. The right hemi-mandibles will be used for detecting of the expression of cytokines, osteoclastogenesis markers and matrix metalloproteinases by real-time polymerase chain reaction (RT-PCR). The results will be analyzed statistically using appropriate tests with a significance level of 5%. (AU)

Scientific publications

(7)

(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)

SILVA, R. A. B.; SOUSA-PEREIRA, A. P.; LUCISANO, M. P.; ROMUALDO, P. C.; PAULA-SILVA, F. W. G.; CONSOLARO, A.; SILVA, L. A. B.; NELSON-FILHO, P.. Alendronate inhibits osteocyte apoptosis and inflammation via IL-6, inhibiting bone resorption in periapical lesions of ovariectomized rats. International Endodontic Journal, v. 53, n. 1, SEP 2019. (14/13238-8, 13/18231-9)

ROMUALDO, PRISCILLA COUTINHO; LUCISANO, MARILIA P.; PAULA-SILVA, FRANCISCO WANDERLEY G.; LEONI, GRAZIELA B.; SOUSA-NETO, MANOEL D.; SILVA, RAQUEL ASSED B.; SILVA, LEA ASSED B.; NELSON-FILHO, PAULO. Ovariectomy Exacerbates Apical Periodontitis in Rats with an Increase in Expression of Proinflammatory Cytokines and Matrix Metalloproteinases. JOURNAL OF ENDODONTICS, v. 44, n. 5, p. 780-785, MAY 2018. (14/13238-8, 13/18231-9)

ROMUALDO, P. C.; CUNHA, N. B. F. F.; LEONI, G. B.; SOUSA-NETO, M. D.; SILVA, R. A. B.; SILVA, L. A. B.; NELSON-FILHO, P.. MICROARCHITECTURE AND BONE MINERAL DENSITY IN FEMURS AND MAXILLAE OF OVARIECTOMIZED RATS SUBJECTED OR NOT TO TREATMENT WITH BISPHOSPHONATE OR A CATHEPSIN K INHIBITOR. OSTEOPOROSIS INTERNATIONAL, v. 28, p. 1-pg., 2017-07-01. (14/13238-8, 13/18231-9)

ROMUALDO, P. C.; LUCISANO, M. P.; PAULA-SILVA, F. W. G.; SILVA, R. A. B.; SILVA, L. A. B.; NELSON-FILHO, P.. ALENDRONATE ATTENUATES THE GENE EXPRESSION OF PROINFLAMMATORY CYTOKINES AND MMP-8 IN APICAL PERIODONTITIS OF OVARIECTOMIZED RATS. OSTEOPOROSIS INTERNATIONAL, v. 29, p. 1-pg., 2018-04-01. (14/13238-8, 13/18231-9)

ROMUALDO, PRISCILLA COUTINHO; FERNANDES FURLANETTO CUNHA, NAYANE BARBOSA; LEONI, GRAZIELA BIANCHI; SOUSA-NETO, MANOEL DAMIAO; CONSOLARO, ALBERTO; DE QUEIROZ, ALEXANDRA MUSSOLINO; BEZERRA DA SILVA, RAQUEL ASSED; BEZERRA DA SILVA, LEA ASSED; NELSON-FILHO, PAULO. The effect of ovariectomy and 2 antiresorptive therapeutic agents on bone response in rats: A 3-dimensional imaging analysis. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 126, n. 3, p. 218-225, SEP 2018. (14/13238-8, 13/18231-9)

LUCISANO, MARILIA PACIFICO; DA SILVA, RAQUEL ASSED BEZERRA; DE SOUSA PEREIRA, ANA PATRICIA; ROMUALDO, PRISCILLA COUTINHO; FERES, MAGDA; DE QUEIROZ, ALEXANDRA MUSSOLINO; NELSON-FILHO, PAULO; DA SILVA, LEA ASSED BEZERRA. Alteration of the oral microbiota may be a responsible factor, along with estrogen deficiency, by the development of larger periapical lesions. CLINICAL ORAL INVESTIGATIONS, v. 25, n. 6, NOV 2020. (14/13238-8, 13/18231-9)

ROMUALDO, P. C.; LUCISANO, M. P.; PAULA-SILVA, F. W. G.; SILVA, R. A. B.; SILVA, L. A. B.; NELSON-FILHO, P.. ALENDRONATE ATTENUATES THE GENE EXPRESSION OF PROINFLAMMATORY CYTOKINES AND MMP-8 IN APICAL PERIODONTITIS OF OSTEOPOROTIC RATS. OSTEOPOROSIS INTERNATIONAL, v. 30, p. 1-pg., 2019-07-01. (14/13238-8, 13/18231-9)