The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue

Autor(es)

Garbieri, Thais Francini ^{[1, 2]} ; Martin, Victor ^{[2, 3]} ; Santos, Carlos Ferreira ^[1] ; Gomes, Pedro de Sousa ^{[2, 3]} ; Fernandes, Maria Helena ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, BR-17012901 Bauru, SP - Brazil

^[2] Univ Porto, Fac Med Dent, Lab Bone Metab & Regenerat, P-4200393 Porto - Portugal

^[3] Univ Porto, LAQV REQUIMTE, P-4160007 Porto - Portugal

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 14, n. 5 MAY 2021.
• Citações Web of Science: 0

Resumo

Activation of renin-angiotensin system (RAS) plays a role in bone deterioration associated with bone metabolic disorders, via increased Angiotensin II (AngII) targeting Angiotensin II type 1 receptor/Angiotensin II type 2 receptor (AT1R/AT2R). Despite the wide data availability, the RAS role remains controversial. This study analyzes the feasibility of using the embryonic chick femur organotypic model to address AngII/AT1R/AT2R axis in bone, which is an application not yet considered. Embryonic day-11 femurs were cultured ex vivo for 11 days in three settings: basal conditions, exposure to AngII, and modulation of AngII effects by prior receptor blockade, i.e., AT1R, AT2R, and AT1R + AT2R. Tissue response was evaluated by combining mu CT and histological analysis. Basal-cultured femurs expressed components of RAS, namely ACE, AT1R, AT2R, and MasR (qPCR analysis). Bone formation occurred in the diaphyseal region in all conditions. In basal-cultured femurs, AT1R blocking increased Bone Surface/Bone Volume (BS/BV), whereas Bone Volume/Tissue Volume (BV/TV) decreased with AT2R or AT1R + AT2R blockade. Exposure to AngII greatly decreased BV/TV compared to basal conditions. Receptor blockade prior to AngII addition prevented this effect, i.e., AT1R blockade induced BV/TV, whereas blocking AT2R caused lower BV/TV increase but greater BS/BV; AT1R + AT2R blockade also improved BV/TV. Concluding, the embryonic chick femur model was sensitive to three relevant RAS research setups, proving its usefulness to address AngII/AT1R/AT2R axis in bone both in basal and activated conditions. (AU)

• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/19227-6 - Investigação da modulação da resposta inflamatória em células orais e imunológicas humanas por Ang II e Ang 1-7
• Beneficiário: Thais Francini Garbieri
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/23934-2 - Papel da angiotensina ii e da angiotensina 1-7 no metabolismo de células ósseas humanas
• Beneficiário: Thais Francini Garbieri
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado