Abstract
Osteoporosis is metabolic bone disease caused by an altered balance between bone anabolism and catabolism. This dysregulated balance is responsible for fragile bones that fracture easily after minor falls. With an aging population, the incidence is rising and as yet pharmaceutical options to restore this imbalance is limited, especially stimulating osteoblast bone-building activity. Excitingly, output from large genetic studies on people with high bone mass (HBM) cases and genome wide association studies (GWAS) on the population, yielded new insights into pathways containing osteo-anabolic players that have potential for drug target development. However, a bottleneck in development of new treatments targeting these putative osteo-anabolic genes is the lack of animal models for rapid and affordable testing to generate functional data and that simultaneously can be used as a compound testing platform. Zebrafish, a small teleost fish, are increasingly used in functional genomics and drug screening assays which resulted in new treatments in the clinic for other diseases. In this review we outline the zebrafish as a powerful model for osteoporosis research to validate potential therapeutic candidates, describe the tools and assays that can be used to study bone homeostasis, and affordable (semi-)high-throughput compound testing.
Highlights
Osteoporosis (OP) is a degenerative bone disease that affects around 27.6 million people over the age of 50 in the 27 European Union (EU27) countries alone [1]
OP is characterized by a reduction in bone mineral density (BMD), reduction of bone mass (BM), and a decrease in the trabecular volume of long bones; resulting in brittle bones that are more prone to fracture [3]
The underlying mechanism behind OP is a dysregulation of bone homeostasis; with decreased bone anabolism and increased catabolism
Summary
Osteoporosis (OP) is a degenerative bone disease that affects around 27.6 million people over the age of 50 in the 27 European Union (EU27) countries alone [1]. Zebrafish are vertebrates and show strong similarities in their skeletal physiology to mammals [23] They are highly fecund and a single pair of fish can lay up to 300 eggs a week, which develop externally and are translucent [24]. The main advantage of zebrafish for functional genetic studies is their genetic tractability, as constructs that modify the genome can be injected directly into embryos at the single cell stage This has allowed the generation of transgenic lines that allow dynamic imaging of all the cells of the developing skeletal system in live larvae [27,28,29] (Table 1) and in more recent years allowed genome editing strategies to be employed. We discuss future prospects for drug screening pipelines in zebrafish which may confer advantages over other pre-clinical model systems
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