Toxins isolated from animal venoms acting on glycation of in vitro osteoarthritis model extracellular matrix

• Grant number: 16/10886-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2016
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: GlaxoSmithKline
• Principal Investigator: Ana Marisa Chudzinski-Tavassi
• Grantee: Maíra Estanislau Soares de Almeida
• Host Institution: Instituto Butantan. 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 (OA) is a multifactorial disease in which age and mechanical stress are important risk factors for this condition. The destruction of cartilage in OA is caused by unbalance in the catabolism and anabolism of chondrocytes resulting in the extracellular matrix (ECM) changed. Glycation is a non-enzymatic reaction that occurs randomly and in pathophysiological processes and is exacerbated with age. In OA the accumulation of Advanced Glycation End Products (AGEs) leads to changes in the composition and structure of the ECM, mainly of collagen type II and aggrecan (negatively charged proteoglycan responsible for attracting water molecules and give the characteristic to absorb shocks and resist compression). These ECM changes result in mechanical failure by altering the microenvironment of the chondrocytes which make up the cartilage matrix, including cytoskeleton and integrin that are mechanosensing molecules. In vitro models are essential to the progress of research for discovering the multifactorial causes of osteoarthritis, as well as for the development of tests with therapeutic potential. The development of biomaterials in vitro to mimic the microenvironment in vivo, as the use of scaffold matrix + cell, has been the target of recent studies in the literature. Associated with this, the use of toxins and molecules derived from animal venom is a broad field of discovery therapeutic targets. The aim of this project is to investigate the actions of the toxins on in vitro model of glycated MEC, which mimics the condition of osteoarthritis pathology. Therefore, this project provides open a new toxins ratio of field of study on the extracellular matrix, in order to aggregate knowledge in the area of biomaterials and new bioproducts. (AU)

Scientific publications

(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)

BUFALO, MICHELLE C.; ALMEIDA, MAIRA E.; FRANCA, ISABELLA ARAUJO; ZAMBELLI, VANESSA O.; SANT'ANNA, MORENA BRAZIL MARTINS; KIMURA, LOUISE F.; GIARDINI, ALINE CAROLINA; CURY, YARA; SAMPAIO, SANDRA COCCUZZO. Advanced glycation endproducts produced by in vitro glycation of type I collagen modulate the functional and secretory behavior of dorsal root ganglion cells cultivated in two-dimensional system. Experimental Cell Research, v. 382, n. 2-3, SEP 15 2019. (16/12128-0, 15/50040-4, 12/51241-5, 16/10886-4)