Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 27;52(2):167-182.e7.
doi: 10.1016/j.devcel.2019.11.016. Epub 2019 Dec 19.

NF-κB Signaling Negatively Regulates Osteoblast Dedifferentiation during Zebrafish Bone Regeneration

Rashmi Mishra  1 , Ivonne Sehring  2 , Maria Cederlund  1 , Medhanie Mulaw  3 , Gilbert Weidinger  4
Affiliations
Free article

NF-κB Signaling Negatively Regulates Osteoblast Dedifferentiation during Zebrafish Bone Regeneration

Rashmi Mishra et al. Dev Cell. .
Free article

Abstract

Dedifferentiation of mature cells is an intriguing cellular process associated with regeneration of several organs. During zebrafish fin regeneration, osteoblasts dedifferentiate to osteogenic progenitors that provide source cells for bone restoration. We performed a high-content in vivo chemical screen for regulators of osteoblast dedifferentiation and fin regenerative growth. NF-κB signaling emerged as a specific regulator of dedifferentiation. The pathway is active in mature osteoblasts and downregulated prior to dedifferentiation. Pathway activation blocked osteoblast dedifferentiation, while NF-κB signaling inhibition enhanced dedifferentiation. Conditional Cre-lox-mediated NF-κB signaling manipulation specifically in osteoblasts showed that the pathway acts cell autonomously to interfere with osteoblast dedifferentiation. NF-κB signaling acts upstream of retinoic acid (RA) signaling, which also needs to be downregulated for dedifferentiation to occur, via suppression of the RA-degrading enzyme cyp26b1. Our findings shed light on the molecular regulation of regenerative cellular plasticity.

Keywords: NF-kappaB; bglap; bone; dedifferentiation; fin; osteoblast; osteocalcin; plasticity; regeneration; zebrafish.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources