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Bisphosphonates and implantology: effects of metalloproteinases inhibitors in in vitro model

Grant number: 19/03261-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Fernanda Gonçalves Basso
Grantee:Luísa Ammirabile Augusto
Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil

Abstract

Bisphosphonates are indicated for the treatment of bone metabolic and neoplastic diseases aiming to control bone resorption. These drugs show high affinity to mineral tissues and are released after traumatic or inflammatory stimuli. Since released, they act by inhibiting osteoclast maturation and inducing apoptosis of these cells. The installation of oral implants in patients on bisphosphonates therapy is controversial since it can result in osteonecrotic lesions. Recent studies demonstrated that these patients can show different clinical outcomes that vary from better osseointegration to implant loss. However, the factor involved on these outcomes is not elucidated. One of these factors is the type of bisphosphonate, directly related to its potency, administration, and dose. These factors can influence the tissue response after implant installation since previous studies showed that these drugs negatively affect the metabolism of mucosa cells inhibiting biological sealing. The super-expression of metalloproteinases (MMP) can also hamper the peri-implant healing. Therefore, the modulation of these enzymes may favor these tissue events. The aim of this study will be to determine the effect of two MMP inhibitors - proanthocyanidin and naringenin - on the viability and synthesis of MMps by gingival fibroblasts exposed do zoledronic acid at different concentrations, Titanium discs will be placed into cell culture plates and cells weill be seeded onto these discs. After 24 hours, bisphosphonate will be added at 0,5, 1 e 5uM. After 48 hours cell viability (alamarBlue) and MMP-2 synthesis (ELISA) will be evaluated.

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