PUBLICATION

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

Authors

Geurtzen, K., Knopf, F., Wehner, D., Huitema, L.F., Schulte-Merker, S., Weidinger, G.

ID

ZDB-PUB-140514-1

Date

2014

Source

Development (Cambridge, England) 141(11): 2225-34 (Journal)

Registered Authors

Huitema, Leonie, Knopf, Franziska, Schulte-Merker, Stefan, Wehner, Daniel, Weidinger, Gilbert

Keywords

none

MeSH Terms

Bone Regeneration
Skull/pathology*
Cell Proliferation
Animal Fins/pathology*
Osteoblasts/cytology*
Osteoblasts/metabolism
Osteogenesis/drug effects
Wound Healing
Animals, Genetically Modified
Necrosis
Luminescent Proteins/metabolism
Zebrafish
Green Fluorescent Proteins/chemistry
Fluorescent Dyes
Animals
Bone and Bones/injuries*
Bone and Bones/pathology*
Cell Differentiation*
Gene Expression Regulation

(all 19)

PubMed

24821985 Full text @ Development

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.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
aldh1a2	WT	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium	ISH	Fig. 1
aldh1a2	WT	surgical manipulation: lepidotrichium segment	Adult	Not Detected	dorsal fin lepidotrichium	ISH	Fig. 1
AmCyan	ulm5Tg	control	Adult		dorsal fin lepidotrichium epidermal cell	ISH	Fig. 1
AmCyan	ulm5Tg	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium	ISH	Fig. 1
bglap	WT	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium	IHC	Fig. 1
bglap	WT	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium	IHC	Fig. 1
bglap	WT	control	Adult		dorsal fin lepidotrichium	IHC	Fig. 1
EGFP	hu4008Tg	control	Adult		dorsal fin lepidotrichium osteoblast	IFL	Fig. 2
EGFP	hu4008Tg	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium osteoblast	IFL	Fig. 2
EGFP	hu4008Tg	surgical manipulation: lepidotrichium segment	Adult		dorsal fin lepidotrichium osteoblast	IFL	Fig. 2

1 - 10 of 71

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium bone regeneration increased process quality, abnormal	Fig. 2
WT	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium osteoblast proliferative, abnormal	Fig. 2
WT	surgical manipulation: lepidotrichium segment	Adult	osteoblast cell dedifferentiation increased occurrence, abnormal	Fig. 2
WT	surgical manipulation: lepidotrichium segment	Adult	osteoblast cell population proliferation increased occurrence, abnormal	Fig. 2
WT	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium bone regeneration increased process quality, abnormal	Fig. 1
hu4008Tg	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium apoptotic process occurrence, normal	Fig. 2
hu4008Tg	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium bone regeneration increased process quality, abnormal	Fig. 2
hu4008Tg	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium bone regeneration increased process quality, abnormal	Fig. 2
hu4008Tg	surgical manipulation: lepidotrichium segment	Adult	dorsal fin lepidotrichium osteoblast poorly differentiated, abnormal	Fig. 2
hu4008Tg	surgical manipulation: lepidotrichium segment	Adult	osteoblast cell dedifferentiation increased occurrence, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type
hu4008Tg	Tg1(Ola.Bglap:EGFP)	Transgenic Insertion
hu6867Tg	TgBAC(entpd5a:Kaede)	Transgenic Insertion
ia5Tg	Tg(7xTCF-Xla.Sia:NLS-mCherry)	Transgenic Insertion
tud8Tg	Tg(Ola.Sp7:Cre-ERT2-2A-mCherry)	Transgenic Insertion
tud9Tg	Tg(hsp70l:LOXP-DsRed2-LOXP-NLS-EGFP)	Transgenic Insertion
ulm5Tg	Tg(krt4:TETAM2-2A-AmCyan)	Transgenic Insertion
zf132Tg	Tg(Ola.Sp7:NLS-GFP)	Transgenic Insertion
zf259Tg	Tg(Hsa.RUNX2-Mmu.Fos:EGFP)	Transgenic Insertion

1 - 8 of 8

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
hu4008Tg
hu6867Tg
ia5Tg
tud8Tg
tud9Tg
ulm5Tg
WT
zf132Tg
zf259Tg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
zns-5	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
AmCyan	EFG	AmCyan
Cre	EFG	Cre
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP
GFP	EFG	GFP
Kaede	EFG	Kaede
mCherry	EFG	mCherry

Mapping

Geurtzen et al., 2014 ZDB-PUB-140514-1 PMID:24821985

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

Geurtzen et al., 2014

ZDB-PUB-140514-1
PMID:24821985