Bothrops moojeni Venom and Its Components Strongly Affect Osteoclasts' Maturation and Protein Patterns

Autor(es)

D'Amelio, Fernanda ^{[1, 2, 3]} ; Vigerelli, Hugo ^{[1, 3]} ; Prieto-da-Silva, Alvaro Rossan de Brandao ^[1] ; Osorio Frare, Eduardo ^{[1, 3]} ; Batista, Isabel de Fatima Correia ^[3] ; Pimenta, Daniel Carvalho ^[4] ; Kerkis, Irina ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Butantan Inst, Genet Lab, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Postgrad Program Toxinol, BR-05503900 Sao Paulo - Brazil

^[3] Butantan Inst, Ctr Excellence New Target Discovery CENTD, BR-05503900 Sao Paulo - Brazil

^[4] Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 13, n. 7 JUL 2021.
• Citações Web of Science: 0

Resumo

Osteoclasts (OCs) are important for bone maintenance, calcium balance, and tissue regeneration regulation and are involved in different inflammatory diseases. Our study aimed to evaluate the effect of Bothrops moojeni's venom and its low and high molecular mass (HMM and LMM) fractions on human peripheral blood mononuclear cell (PBMC)-derived OCs' in vitro differentiation. Bothrops moojeni, a Brazilian lanced-head viper, presents a rich but not well-explored, venom composition. This venom is a potent inducer of inflammation, which can be used as a tool to investigate the inflammatory process. Human PBMCs were isolated and induced to OC differentiation following routine protocol. On the fourth day of differentiation, the venom was added at different concentrations (5, 0.5, and 0.05 mu g/mL). We observed a significant reduction of TRAP+ (tartrate-resistant acid phosphatase) OCs at the concentration of 5 mu g/mL. We evaluated the F-actin-rich OCs structure's integrity; disruption of its integrity reflects bone adsorption capacity. F-actin rings phalloidin staining demonstrated that venom provoked their disruption in treated OCs. HMM, fraction reduces TRAP+ OCs at a concentration of 5 mu g/mL and LMM fraction at 1 mu g/mL, respectively. Our results indicate morphological changes that the venom induced cause in OCs. We analyzed the pattern of soluble proteins found in the conditioned cell culture medium OCs treated with venom and its fractions using mass spectrometry (LC-MS/IT-Tof). The proteomic analyses indicate the possible pathways and molecular mechanisms involved in OC reduction after the treatment. (AU)

• Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Beneficiário: Ana Marisa Chudzinski-Tavassi
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia