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Several studies have shown that chondrocyte aging is associated with the degeneration of articular cartilage, and can be observed in joint diseases pathogenesis, such as rheumatoid arthritis and osteoarthritis (OA). one of the most prominent changes in

Grant number: 18/20469-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Biochemistry
Cooperation agreement: GlaxoSmithKline
Principal Investigator:Ana Marisa Chudzinski-Tavassi
Grantee:Renata Nascimento Gomes
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

Several studies have shown that chondrocyte aging is associated with the degeneration of articular cartilage, and can be observed in joint diseases pathogenesis, such as rheumatoid arthritis and osteoarthritis (OA). One of the most prominent changes in cartilage is related to extracellular matrix components. Moreover, pro-inflammatory cytokines, such as TNF-alpha and IL-1², play pivotal roles in the progression of these degenerative changes. Losac (Lonomia obliqua Stuart-factor ACtivator) is a component of the bristle of L. obliqua that shares different degrees of similarity with cell adhesion molecules members of the immunoglobulin superfamily (IgSF). Previously, it was shown that Losac induces a pro-survival activity in serum-deprived HUVECs by increasing mitochondria metabolism. All of our analyses indicate that, Losac trigger cell viability through the stimulation or activation of survival/proliferative pathways (ERK1/2 MAPK) in the early hours of cell contact with Losac and subsequent gene expression, DNA synthesis and proliferation. It is worthwhile noting that microarray analysis (in endothelial cells) pointed the involvement of PDGFR (platelet-derived growth factor receptor) in Losac-induced cell survival. In fibroblast, rLosac stimulate cell survival but not cell proliferation, suggesting different effects depending on the cellular type. Recently, preliminary data from an in vivo model of wound healing has shown rLosac to induce collagen synthesis in rat dermis. On the other hand, Lopap (Lonomia obliqua prothrombin activator protein) was isolated from bristles of Lonomia obliqua caterpillar, and belongs to the lipocalins family. The recombinant form (rLopap) displays serine protease-like activity with effects on different cells, including chondrocytes, acting promoting antiapoptotic effects even under stress conditions (as inflammation process), and increases the expression of molecules involved in tissue remodeling (as collagen, fibronectin and tenascin). Taken all findings together, rLosac and rLopap might have potential to prevent inflammation, aging, and cellular death induced in pro-inflammatory chondrocytes. Those proteins and the bristle extract of Lonomia obliqua could be considered as a promising tool for studies of targets protecting articular cartilage against OA progression.