title: Mature osteoblasts dedifferentiate in response to traumatic bone injury in the zebrafish fin and skull.
abstract: Zebrafish have an unlimited capacity to regenerate bone after fin amputation. In this process, mature osteoblasts dedifferentiate to osteogenic precursor cells and thus represent an important source of newly forming bone. By contrast, differentiated osteoblasts do not appear to contribute to repair of bone injuries in mammals; rather, osteoblasts form anew from mesenchymal stem cells. This raises the question whether osteoblast dedifferentiation is specific to appendage regeneration, a special feature of the lepidotrichia bone of the fish fin, or a process found more generally in fish bone. Here, we show that dedifferentiation of mature osteoblasts is not restricted to fin regeneration after amputation, but also occurs during repair of zebrafish fin fractures and skull injuries. In both models, mature osteoblasts surrounding the injury downregulate the expression of differentiation markers, upregulate markers of the pre-osteoblast state and become proliferative. Making use of photoconvertible Kaede protein as well as Cre-driven genetic fate mapping, we show that osteoblasts migrate to the site of injury to replace damaged tissue. Our findings suggest a fundamental role for osteoblast dedifferentiation in reparative bone formation in fish and indicate that adult fish osteoblasts display elevated cellular plasticity compared with mammalian bone-forming cells.
authors.affiliation: Biotechnology Center and CRTD, Technische Universität Dresden, 01307 Dresden, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Geurtzen
authors.affiliation: Biotechnology Center and CRTD, Technische Universität Dresden, 01307 Dresden, Germany Kennedy Institute of Rheumatology, Oxford OX3 7FY, UK.
authors.forename: Franziska
authors.initials: F
authors.lastname: Knopf
authors.affiliation: Institute for Biochemistry and Molecular Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehner
authors.affiliation: Hubrecht Institut-KNAW & UMC Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Leonie F A
authors.initials: LF
authors.lastname: Huitema
authors.affiliation: Hubrecht Institut-KNAW & UMC Utrecht, 3584 CT Utrecht, The Netherlands EZO, WUR, 6709 PG Wageningen, The Netherlands Institute of Cardiovascular Organogenesis and Regeneration, University of Münster, 48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulte-Merker
authors.affiliation: Institute for Biochemistry and Molecular Biology, Ulm University, 89081 Ulm, Germany gilbert.weidinger@uni-ulm.de.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Weidinger
mesh_terms: D058500:Animal Fins / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D001861:Bone Regeneration; D001842:Bone and Bones / Q000293:injuries* / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000737:chemistry; D008164:Luminescent Proteins / Q000378:metabolism; D009336:Necrosis; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D012886:Skull / Q000473:pathology*; D014945:Wound Healing; D015027:Zebrafish
chemical_list: D005456:Fluorescent Dyes; C513582:Kaede protein, Trachyphyllia geoffroyi; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins
keywords: Bone; Dedifferentiation; Fracture; Injury; Kaede; Lepidotrichia; Osteoblast; Osteocalcin; Skull; Zebrafish