I. Componente Universitária
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Browsing I. Componente Universitária by advisor "Abellán, Francisco António Guardiola"
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- The influence of inflammatory processes in fish skeletal development: the crosstalk between skeletal and immune systemsPublication . Martins, Gil Sales Marques; Gavaia, Paulo Jorge Travessa; Abellán, Francisco António GuardiolaOsteoimmunology is an emerging field focused on the comprehension of the crosstalk between the immune and skeletal systems, with a particular focus on how inflammation affects bone health and disease. Previous research suggests that the same signalling mechanism that occurs in mammals may trigger the differentiation of macrophages into osteoclasts in teleosts, leading to the onset of pathological bone resorption by an identical molecular process. However, little is known about the contribution of the inflammatory processes and or bacterial constituents in fish bone tissues. In this thesis, we tackle this issue by evaluating the impact of continuous exposure to bacterial lipopolysaccharides (LPS) in zebrafish dermal skeleton (scales) and evaluating the potential of the microalga Tisochrysis lutea ethanolic extract and its glycolipid (GL) fractions to reverse the LPS effects. The continuous exposure to LPS led to the reduction of de novo formed scales and led to scale demineralization, with increased osteoclast activity, and inflammatory and osteoclastic marker genes (i.e., tnfa, ctsk, and acp5). In ex vivo cultured scales, LPS led to an increase in the number of osteoclast areas, while reducing the number of macrophages. An overlap between cell types and TRAP+ signals indicates the possible differentiation of macrophages into osteoclasts. T. lutea extract and two isolated glycolipid fractions (Tl-glF1 and Tl-glF2) evidenced an anti-osteoclastic potential against the differentiation of RAW 264.7-derived osteoclasts (RAW-Ocs), with a reduced number of mono- and multinucleated osteoclasts. The data collected in this thesis supports the use of zebrafish scales exposed to LPS at 10 μg mL-1 as an in vivo and ex vivo screening method for searching novel anti-resorptive compounds for inflammatory diseases, to study the mechanisms involved in increased bone resorption, and the role of LPS in the differentiation of macrophages into osteoclasts. T. lutea GLs contain anti-resorptive properties and should be further investigated for their application in osteoimmune diseases.
