Mature osteoblasts dedifferentiate in response to traumatic bone injury in the zebrafish fin and skull

Karina Geurtzen, Franziska Knopf, Daniel Wehner, Leonie F A Huitema, Stefan Schulte-Merker, Gilbert Weidinger

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)2225-34
Number of pages10
JournalDevelopment
Volume141
Issue number11
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Animal Fins
  • Animals
  • Animals, Genetically Modified
  • Bone Regeneration
  • Bone and Bones
  • Cell Differentiation
  • Cell Proliferation
  • Fluorescent Dyes
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Luminescent Proteins
  • Necrosis
  • Osteoblasts
  • Osteogenesis
  • Skull
  • Wound Healing
  • Zebrafish

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