title: Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin.
abstract: While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is derived from, whether it forms by dedifferentiation of mature cells, and whether blastema cells are multipotent. We show that mature osteoblasts dedifferentiate and form part of the blastema. Osteoblasts downregulate expression of intermediate and late bone differentiation markers and induce genes expressed by bone progenitors. Dedifferentiated osteoblasts proliferate in a FGF-dependent manner and migrate to form part of the blastema. Genetic fate mapping shows that osteoblasts only give rise to osteoblasts in the regenerate, indicating that dedifferentiation is not associated with the attainment of multipotency. Thus, bone can regenerate from mature osteoblasts via dedifferentiation, a finding with potential implications for human bone repair.
authors.affiliation: Biotechnology Center and Center for Regenerative Therapies, University of Technology Dresden, Tatzberg 47-49, 01307 Dresden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Knopf
authors.forename: Christina
authors.initials: C
authors.lastname: Hammond
authors.forename: Avinash
authors.initials: A
authors.lastname: Chekuru
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurth
authors.forename: Stefan
authors.initials: S
authors.lastname: Hans
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Weber
authors.forename: Gina
authors.initials: G
authors.lastname: Mahatma
authors.forename: Shannon
authors.initials: S
authors.lastname: Fisher
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulte-Merker
authors.forename: Gilbert
authors.initials: G
authors.lastname: Weidinger
mesh_terms: D058500:Animal Fins / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D054337:Cell Dedifferentiation; D015536:Down-Regulation; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015027:Zebrafish