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=== Bone physiology and pathology === Zebrafish have been used as model organisms for bone metabolism, tissue turnover, and resorbing activity. These processes are largely evolutionary conserved. They have been used to study osteogenesis (bone formation), evaluating differentiation, matrix deposition activity, and cross-talk of skeletal cells, to create and isolate mutants modeling human bone diseases, and test new chemical compounds for the ability to revert bone defects.<ref>{{cite journal |vauthors=Witten PE, Hansen A, Hall BK |title=Features of mono- and multinucleated bone resorbing cells of the zebrafish Danio rerio and their contribution to skeletal development, remodeling, and growth |journal=Journal of Morphology |volume=250 |issue=3 |pages=197β207 |date=December 2001 |pmid=11746460 |doi=10.1002/jmor.1065 |s2cid=33403358}}</ref><ref>{{cite journal |vauthors=Carnovali M, Banfi G, Mariotti M |title=Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together |journal=BioMed Research International |volume=2019 |page=1253710 |year=2019 |pmid=31828085 |pmc=6886339 |doi=10.1155/2019/1253710 |doi-access=free}}</ref> The larvae can be used to follow new (''de novo'') osteoblast formation during bone development. They start mineralising bone elements as early as 4 days post fertilisation. Recently, adult zebrafish are being used to study complex age related bone diseases such as [[osteoporosis]] and [[osteogenesis imperfecta]].<ref name=":1">{{cite journal |vauthors=Bergen DJ, Kague E, Hammond CL |title=Zebrafish as an Emerging Model for Osteoporosis: A Primary Testing Platform for Screening New Osteo-Active Compounds |journal=Frontiers in Endocrinology |volume=10 |page=6 |date=2019 |pmid=30761080 |pmc=6361756 |doi=10.3389/fendo.2019.00006 |doi-access=free}}</ref> The (elasmoid) [[Fish scale#Elasmoid scales|scales]] of zebrafish function as a protective external layer and are little bony plates made by osteoblasts. These exoskeletal structures are formed by bone matrix depositing osteoblasts and are remodeled by osteoclasts. The scales also act as the main calcium storage of the fish. They can be cultured ex-vivo (kept alive outside of the organism) in a multi-well plate, which allows manipulation with drugs and even screening for new drugs that could change bone metabolism (between osteoblasts and osteoclasts).<ref name=":1" /><ref>{{cite journal |vauthors=de Vrieze E, van Kessel MA, Peters HM, Spanings FA, Flik G, Metz JR |title=Prednisolone induces osteoporosis-like phenotype in regenerating zebrafish scales |journal=Osteoporosis International |volume=25 |issue=2 |pages=567β578 |date=February 2014 |pmid=23903952 |doi=10.1007/s00198-013-2441-3 |s2cid=21829206|hdl=2066/123472 |hdl-access=free}}</ref><ref>{{cite journal |vauthors=de Vrieze E, Zethof J, Schulte-Merker S, Flik G, Metz JR |title=Identification of novel osteogenic compounds by an ex-vivo sp7:luciferase zebrafish scale assay |journal=Bone |volume=74 |pages=106β113 |date=May 2015 |pmid=25600250 |doi=10.1016/j.bone.2015.01.006 |hdl=2066/153047 |hdl-access=free}}</ref>
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