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1. Silva, Jo�o Pedro Gon�alves Cardeira da. Mechanisms of de novo bone formation in a fish model of fin regenaration.

Degree: 2018, RCAAP

Unveiling the basis of animal tissue regeneration may contribute to the better understanding of disease mechanisms and the development of novel therapeutic strategies. Regeneration-competent animals are also valuable tools in drug discovery and for studying basic mechanisms of development. Bone is a dynamic tissue, formed and maintained through a balance between matrix deposition by osteoblasts and resorption by osteoclasts. When bone remodelling fails to homeostatic equilibrium, degenerative and dysplastic diseases may develop. Moreover, human bone is unable to completely restore structure and function after trauma. Hence, this work aimed at uncovering novel players in bone formation and patterning in an innovative system, the zebrafish regenerating caudal fin. A comprehensive set of imaging and analytical methodologies were first development and optimized to track bone formation and regeneration in a precise and timely manner throughout fin epimorphic regeneration. To gain insights into cellular and molecular programs underlying bone regeneration, the transcriptome of regenerates at distinct stages (blastema formation and regenerative outgrowth) was analysed. RNA-Seq data pointed toward a role of osteoclasts and calcitonin in ray patterning. Calcitonin-specific inhibition of osteoclast activity impaired ray bifurcation and demonstrated the central role that osteoclasts play in this process. Evidence toward calcitonin-specific regulation of osteoclast differentiation in the context of ray bifurcation, was also collected. To further study the mechanisms underlying bone formation, a swim-training regeneration model was established. In this model, bone formation during regeneration was stimulated and ray bifurcation was accelerated upon increased mechanical loading, further demonstrating the suitability of this system to investigate underlying mechanisms. This work provided valuable technical advancements for the study of bone regeneration in zebrafish and identified novel players in ray formation and patterning (i.e. bifurcation). Altogether, this work also proposes the zebrafish bifurcating fin ray as a potential model for tetrapod digit specification and associated diseases.

Desvendar a base dos mecanismos de regenera��o de tecidos animais poder� contribuir para compreender mecanismos de doen�a e desenvolver estrat�gias terap�uticas. Os animais capazes de regenerar �rg�os e tecidos s�o, tamb�m, ferramentas-chave para a descoberta de f�rmacos e para o estudo de mecanismos b�sicos de desenvolvimento. O osso � um tecido altamente din�mico, sendo formado e mantido atrav�s de um balan�o entre os processos de deposi��o de matriz por osteoblastos e reabsor��o por osteoclastos. Uma desregula��o deste equil�brio homeost�tico no processo de remodela��o �ssea pode levar a v�rias doen�as degenerativas e displ�sticas. Para al�m disso, o osso humano, apesar de reparar, n�o tem a capacidade de restaurar eficientemente a estrutura e fun��o ap�s trauma. Ao contr�rio dos mam�feros, o peixe-zebra tem a capacidade de regenerar…

Advisors/Committee Members: Laiz�, Vicent St�phanie, Gavaia, Paulo Jorge.

Subjects/Keywords: Sistema de regenera��o da barbatana caudal do peixe-zebra; Colora��o com vermelho de alizarina S; Osteoclastos; Bifurca��o dos raios; Calcitonina; Mecanofisiologia; Dom�nio/�rea Cient�fica::Ci�ncias M�dicas::Medicina Cl�nica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Silva, J. P. G. C. d. (2018). Mechanisms of de novo bone formation in a fish model of fin regenaration. (Thesis). RCAAP. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/10767

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Silva, Jo�o Pedro Gon�alves Cardeira da. “Mechanisms of de novo bone formation in a fish model of fin regenaration.” 2018. Thesis, RCAAP. Accessed April 10, 2020. https://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/10767.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Silva, Jo�o Pedro Gon�alves Cardeira da. “Mechanisms of de novo bone formation in a fish model of fin regenaration.” 2018. Web. 10 Apr 2020.

Vancouver:

Silva JPGCd. Mechanisms of de novo bone formation in a fish model of fin regenaration. [Internet] [Thesis]. RCAAP; 2018. [cited 2020 Apr 10]. Available from: https://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/10767.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Silva JPGCd. Mechanisms of de novo bone formation in a fish model of fin regenaration. [Thesis]. RCAAP; 2018. Available from: https://www.rcaap.pt/detail.jsp?id=oai:sapientia.ualg.pt:10400.1/10767

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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