Fish models of induced osteoporosis

Osteopenia and osteoporosis are bone disorders characterized by reduced bone mineral density (BMD), altered bone microarchitecture and increased bone fragility. Because of global aging, their incidence is rapidly increasing worldwide and novel treatments that would be more efficient at preventing disease progression and at reducing the risk of bone fractures are needed. Preclinical studies are today a major bottleneck to the collection of new data and the discovery of new drugs, since they are commonly based on rodent in vivo systems that are time consuming and expensive, or in vitro systems that do not exactly recapitulate the complexity of low BMD disorders. In this regard, teleost fish, in particular zebrafish and medaka, have recently emerged as suitable alternatives to study bone formation and mineralization and to model human bone disorders. In addition to the many technical advantages that allow faster and larger studies, the availability of several fish models that efficiently mimic human osteopenia and osteoporosis phenotypes has stimulated the interest of the academia and industry toward a better understanding of the mechanisms of pathogenesis but also toward the discovery of new bone anabolic or antiresorptive compounds. This mini review recapitulates the in vivo teleost fish systems available to study low BMD disorders and highlights their applications and the recent advances in the field.UIDB/04326/2020, EAPA_151/2016/BLUEHUMANinfo:eu-repo/semantics/publishedVersio

Expression of Gla proteins during fish skeletal development

Senegal sole skeletal development; Skeletal malformations; Skeletal malformation in mediterranean species; Senegal sole skeletal deformities; Zebra fish as model system: skeletal development; Identification of bone cells / skeletal development; Spatial - temporal pattern of bgp expression; Single cell resolution: localization of bgp mRNA; Single cell resolution: Immunolocalization of Bgp; Single cell resolution: localization of mgp mRNA; Single cell resolution: Immunolocalization of Mgp; An in vivo system to uncover MGP and BGP function; Effects of warfarin on toadfish

Functional analysis of bone related Gla proteins from bony fish during skeletal development

Tese de Doutoramento, Biologia, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2005As proteinas dependentes da vitamina K, proteína Gla do osso (BGP ou osteocalcina) e proteína Gla da matriz (MGP) são pequenas proteinas que ligam o cálcio, tendo sido recentemente descobertas em peixe.The vitamin K dependent bone Gla protein (BGP or osteocalcin) and matrix Gla protein (MGP) are small calcium binding proteins only recently discovered in fish

Temporal and spatial expression patterns of pregnane X receptor and vitamin K epoxide reductase genes, two core molecular players on fish vitamin K homeostasis and skeletal development.

Vitamin K (VK) is a liposoluble vitamin known to be essential for bone metabolism by two different pathways: (i) by its role as a coenzyme in the gamma-carboxylation of some skeletal proteins (e.g. osteocalcin (OC) and matrix Gla protein (MGP); Price et al., 1998); and (ii) through its role in skeletal gene transcription via binding to the pregnane X receptor (PXR; Azuma et al., 2010)

Gene expression during regeneration of zebrafish (danio rerio) fins: relative expression levels of mineralization – related gla proteins

Most animals have the ability to regenerate epidermal injuries yet only a few can regenerate largely severed appendages that comprise several different tissues. Nowadays zebrafish is one of the most used metazoan models in regeneration studies in particular for investigation of molecular events during fin regeneration process. Fin regeneration starts through the formation of a blastema, a set of heterogeneous mesenchyma-like cells located between stump tissues and the wounded epidermis. This event, denominated epimorphic regeneration, comprises strict growth control and cell reprogramming leading to faithful restoration of the lost parts

Skeletal development and bone-related gene expression in fish larvae

The fish skeleton; skeletal malformations; skeletal malformations in mediterranean species; Types of skeletal malformations; Senegal sole skeletal development; Senegal sole skeletal deformities; Skeletal development in Danio rerio; ALP and TRAP in skeletal development; Skeletal development in Pagrus auriga; Time course of skeletal development in Pagrus auriga; Spatio-temporal pattern of bgp expression; bgp / mgp expression during development; In situ localization of zebrafish bgp mRNA;In situ localization of sole bgp mRNA; Immuno-detection of Bgp accumulation in zebrafish; Immuno-detection of Bgp accumulation in sole P.; In situ localization of zebrafish and sole mgp mRNA; Immuno-detection of MGP accumulation in zebrafish; Summary of zebrafish skeletogenesis; Summary of Senegal sole skeletogenesis; In situ localization of zebrafish CollX1 mRNA

Localization of osteocalcin (BGP) during fish (Sparus aurata) development by in situ hybridization and immunohistochemistry: comparison between gene expression/protein distribution and skeletal mineralization

Osteocalcin (Bone Gla protein, BGP) is a small noncollagenous protein which is synthesized by osteoblasts and odontoblasts and is found exlusively in mineralized bony tissues. Although isolated for the first time in 1978, only recently has a function for this protein been suggested, specifically in controlling hydroxyapatite crystal growth. Appearance of osteocalcin could be linked to the presence of an hydroxyapatite-containing bony skeleton, since the protein was never found in cartilaginous fishes. Furthermore, within its primary sequence the amino acid residues known to be essential for its function are present in fish as well as in mammals, suggesting that function has been conserved over 400 million years of evolution. Taken totgether, these findings prompted us to study in detail the localization of osteocalcin gene expression in fish

Review of the principal diseases affecting cultured meagre (Argyrosomus regius)

Argyrosomus regius was recently introduced in European aquaculture as a promising species for diversification and with high potential for expansion in the coming years. The reports on pathologies affecting this species are still scarce in the bibliography, however, they can severely affect production and result in major economic losses. Some few reports were made on outbreaks and mortalities associated with the presence of bacteria such as Vibrio anguillarum and Photobacterium damselae subsp. piscicida. Although no viral diseases have been recognized as affecting meagre, it is known that meagre can be an asymptomatic carrier of two genotypes of nodavirus, the striped jack nervous necrosis virus and red‐spotted grouper nervous necrosis virus. Up‐to‐date, parasites affecting meagre are included in the genera Monogenea, Nematoda and Dinoflagelate, but without major mortality outbreaks associated to this type of infections. Osteological deformities have been observed in all life stages particularly affecting the axial system in larval and early juvenile specimens, with a higher incidence in the vertebral column, being affected by vertebral fusions, lordosis and kyphosis. With this review the authors provide an overview of all the pathological and non‐pathological diseases affecting aquaculture produced meagre and provide a comprehensive overview of possible problems for the industry.info:eu-repo/semantics/acceptedVersio

Screening of mineralogenic and osteogenic compounds in zebrafish—tools to improve assay throughput and data accuracy

Bone disorders affect millions of people worldwide and treatments currently available often produce undesirable secondary effects or have limited efficacy. It is therefore of the utmost interest for patients to develop more efficient drugs with reduced off-target activities. In the long process of drug development, screening and preclinical validation have recently gained momentum with the increased use of zebrafish as a model organism to study pathological processes related to human bone disorders, and the development of zebrafish high-throughput screening assays to identify bone anabolic compounds. In this review, we provided a comprehensive overview of the literature on zebrafish bone-related assays and evaluated their performance towards an integration into screening pipelines for the discovery of mineralogenic/osteogenic compounds. Tools available to standardize fish housing and feeding procedures, synchronize embryo production, and automatize specimen sorting and image acquisition/analysis toward faster and more accurate screening outputs were also presented.info:eu-repo/semantics/publishedVersio

Zebrafish models to study ectopic calcification and calcium-associated pathologies

Ectopic calcification refers to the pathological accumulation of calcium ions in soft tissues and is often the result of a dysregulated action or disrupted function of proteins involved in extracellular matrix mineralization. While the mouse has traditionally been the go-to model organism for the study of pathologies associated with abnormal calcium deposition, many mouse mutants often have exacerbated phenotypes and die prematurely, limiting the understanding of the disease and the development of effective therapies. Since the mechanisms underlying ectopic calcification share some analogy with those of bone formation, the zebrafish (Danio rerio)—a well-established model for studying osteogenesis and mineralogenesis—has recently gained momentum as a model to study ectopic calcification disorders. In this review, we outline the mechanisms of ectopic mineralization in zebrafish, provide insights into zebrafish mutants that share phenotypic similarities with human pathological mineralization disorders, list the compounds capable of rescuing mutant phenotypes, and describe current methods to induce and characterize ectopic calcification in zebrafish.info:eu-repo/semantics/publishedVersio