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Signaling pathways involved in the inflammatory response in cellular osteoarthritis models

Grant number: 19/09498-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2019
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Immunology
Cooperation agreement: GlaxoSmithKline
Principal Investigator:Denise Vilarinho Tambourgi
Grantee:Paula Cristiane Pohl
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival, AP.PCPE

Abstract

Osteoarthritis is a chronic degenerative disease of the joint, characterized by progressive degradation of cartilage and bone damage, and the mechanisms that drive it are widely investigated. The events can produce irreversible calcification of the matrix cartilage and the induction of the expression of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and apoptotic factors by synovial cell and chondrocytes. In osteoarthritis, some cytokines appear to be more produced by cartilage than by the synovial tissue. Thus, the degradation of cartilage with secondary synovitis is considered the main pathological characteristic of joints in osteoarthritis.The inflammatory response involved in osteoarthritis will be studied in cellular models, including chondrocytes and human synoviocytes. Cultures will be stimulated by toxins isolated from animal poisons, whose proinflammatory activities have been previously described, and the expression and production of molecules involved with inflammation will be evaluated.After this initial screening in vitro, some toxins will be chosen to better elucidate the signaling pathways triggered in the different cell types. The study of signaling pathways will involve different assays, such as the use of specific inhibitors and the intracellular staining of signaling molecules, which will be analyzed by multicolor flow cytometry and confocal microscopy, including evaluation of the co-localization of markers. These studies will allow the identification of new signaling molecules involved with the inflammatory response and possibly new targets for the development of specific anti-inflammatory drugs for the treatment of osteoarthritis.