Therapeutic epigenomic targets: MiRNA profile in an in vitro model of osteoarthritis treated with rLosac (PD-1)

• Grant number: 16/11965-5
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2016
• Effective date (End): April 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Cooperation agreement: GlaxoSmithKline
• Principal researcher: Ana Marisa Chudzinski-Tavassi
• Grantee: Carlos Deocesano-Pereira
• 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

MicroRNAs are evolutionary conserved and the ubiquitous class of small non-codings RNAs, with 20-23 nucleotides on average, broadly expressed in different cell types and tissues [1]. They play crucial regulatory role in a variety of metabolic pathways, cellular events and physiological process, such as immune response, pathogenesis of cancer and inflammatory-related diseases, including osteoarthritis, rheumatoid arthritis and neuroinflammatory conditions. A large body of literature establishes that chondrocytes aging is associated with the degeneration of articular cartilage, which is commonly observed in the pathogenesis of joint diseases, such as rheumatoid arthritis and osteoarthritis (OA). In preliminary in vitro studies with isolated chondrocytes, rLosac (a recombinant form of the protein isolated from Lonomia obliqua caterpillar) has been found to be an effective anti-apoptotic agent and has cytoprotective effect in 48h and 72h treatments. Moreover, rLosac was able to reduce the IL-1²-induced expression of ²-galactosidade, suggesting that rLosac may have the potential to prevent the features of senescence in OA chondrocytes. Considering the protective effects of rLosac in this model of OA and the possible involvement of miRNAs in the regulation of these pathways, the main objective of this project is to determine a miRNA profile in chondrocytes treated with rLosac for determining the activated pathways for cytoprotection and to relate with probable targets for osteoarthritis. (AU)