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INSIGHTS INTO MOLECULAR AND CELULLAR EVENTS INVOLVED IN HUMAN PATHOLOGICAL FUSION OF VERTEBRAL JOINTS THROUGH THE USE OF ZEBRAFISH AS MODEL ORGANISM

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Skeletal development and performance of zebrafish Danio rerio (Hamilton, 1822) larvae and juvenile fish fed with different diets
Publication . Cardeira Da Silva, João; Dionísio, Gisela; Bensimon-Brito, A.; Cancela, Leonor; Gavaia, Paulo J.
The appearance of skeletal deformities is a major problem associated to intensive, large-scale culture of fish species, affecting growth, development and ultimately, survival of produced fish. Although the mechanisms working behind it are still unclear, it is known that environmental, genetic and nutritional factors play fundamental roles. Given its importance as a vertebrate model to study skeleton-related diseases, the selection of an appropriate dietary protocol is a critical step in order to diminish the nutritional effect on bone and cartilage development.
Warfarin effects in the skeletal development of zebrafish (Danio rerio)
Publication . Peres dos Santos, R.; Bensimon-Brito, A.; Gavaia, Paulo J.; Cancela, Leonor
Vitamin K-dependent gamma carboxylation (VKGC) is crucial for posttranslational modification of glutamate residues to form α-carboxy glutamic acid (Gla) in the presence of reduced vitamin K, molecular oxygen, and carbon dioxide (1). This modification has important implications, mainly physiological, like homeostasis, signal transduction and bone calcification. This mechanism ensures complete carboxylation of coagulation factors, and proteins like bone Gla protein (BGP) and matrix Gla protein (MGP), being essential for their biological activity. Warfarin is a known anticoagulant that inhibits the action of VKGC (2), inhibiting consequently the activity of the referred proteins.
Effect of warfarin in zebrafish (Danio rerio) bone formation during caudal fin regeneration
Publication . Dionísio, Gisela; Bensimon-Brito, A.; Gavaia, Paulo J.; Cancela, Leonor
In the last decade, fish has emerged as an important organism for studies on skeletal development in vertebrates, and evidence has been accumulated showing that zebrafish is a suitable system to perform phenotype-based drug screens. The ability to regenerate epidermal injuries is a general feature of most organisms yet only a few can fully regenerate severed appendages comprising several different tissues. Zebrafish is one of the most used models for regeneration studies, creating a powerful tool to study de novo bone formation without affecting vital development processes.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

PIDDAC

Funding Award Number

SFRH/BD/40573/2007

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