Skeletal Biology and Disease Modeling in Zebrafish

Abstract

Zebrafish are teleosts (bony fish) that share with mammals a common ancestor belonging to the phylum Osteichthyes, from which their endoskeletal systems have been inherited. Indeed, teleosts and mammals have numerous genetically conserved features in terms of skeletal elements, ossification mechanisms, and bone matrix components in common. Yet differences related to bone morphology and function need to be considered when investigating zebrafish in skeletal research. In this review, we focus on zebrafish skeletal architecture with emphasis on the morphology of the vertebral column and associated anatomical structures. We provide an overview of the different ossification types and osseous cells in zebrafish and describe bone matrix composition at the microscopic tissue level with a focus on assessing mineralization. Processes of bone formation also strongly depend on loading in zebrafish, as we elaborate here. Furthermore, we illustrate the high regenerative capacity of zebrafish bones and present some of the technological advantages of using zebrafish as a model. We highlight zebrafish axial and fin skeleton patterning mechanisms, metabolic bone disease such as after immunosuppressive glucocorticoid treatment, as well as osteogenesis imperfecta (OI) and osteopetrosis research in zebrafish. We conclude with a view of why larval zebrafish xenografts are a powerful tool to study bone metastasis. © 2021 American Society for Bone and Mineral Research (ASBMR).

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

“…To investigate the role of ALDH1A1 and ALDH1A3 for tumor cell survival in the blood stream and during the extravasation process in vivo, we implemented the Zebrafish (Danio rerio) model to xenograft with human prostate cells. Zebrafish represent a powerful tool for cancer research: human and zebrafish genomes share gene orthology for 82% of disease-causing genes (Amawi et al, 2021;Howe et al, 2013;Letrado et al, 2018;Terriente and Pujades, 2013), and transparent embryos can be injected with cancer cells at various locations, allowing the live observation of tumor cells (Dietrich et al, 2021). In our study, we have used the embryonic and larval in vivo model to analyze the role of ALDH1A1 and ALDH1A3 genes in human cancer dissemination.…”

Zebrafish Models for Human Skeletal Disorders

“…Osteoporotic drug testing in zebrafish started by the need to study the osteoporotic effects of glucocorticoids in patients under immunosuppressive treatments. The hormonal response of zebrafish to glucocorticoids mimics that shown by humans, providing an interesting non-genetic model for bone formation, mineralization, and osteoclast activity ( Dietrich et al, 2021 ). Once dexamethasone or prednisolone is added to water, osteoporosis is induced in zebrafish, and potential preventing drugs can be tested ( Dietrich et al, 2021 ).…”

“…Once dexamethasone or prednisolone is added to water, osteoporosis is induced in zebrafish, and potential preventing drugs can be tested (Dietrich et al, 2021). Fluorescent calcein staining has also been used to test calcification in wild-type strains in standard conditions or during bone fracture modeling (Bae et al, 2017;Son et al, 2019;Tomecka et al, 2019).…”

“…Many reviews have recently been published to address the use of zebrafish models of skeletal disorders. In these reviews, genetic ( Eisen and Smith, 2008 ; Auer and Del Bene, 2014 ; Kwon et al, 2019 ; Tonelli et al, 2020a ; Dietrich et al, 2021 ) and phenotyping ( Kwon et al, 2019 ; Busse et al, 2020 ; Tonelli et al, 2020a ) methods and many of available models have been described ( Luderman et al, 2017 ; Carnovali et al, 2019 ; Kwon et al, 2019 ; Busse et al, 2020 ; Tonelli et al, 2020a ; Dietrich et al, 2021 ). Nevertheless, no review has updated this rapidly growing field under the directives of the NCGSD.…”

Fish Models of Induced Osteoporosis

“…In addition to the above-mentioned models, morphants, stable knockdown and mutant zebrafish lines displaying phenotypic features that partially mimic OP are available (they have been extensively discussed by Laizé et al, 2014 ; Bergen et al, 2019 ; Carnovali et al, 2019a ; Tonelli et al, 2020 ; Dietrich et al, 2021 ). These models are valuable tools to study OP-related genes and mechanisms associated with low BMD and fragile bones, and can be used in compound screening assays.…”