Next Article in Journal
The Potential of the Cyclotide Scaffold for Drug Development
Previous Article in Journal
Hepatoprotective Activity of InlB321/15, the HGFR Ligand of Bacterial Origin, in CCI4-Induced Acute Liver Injury Mice
Previous Article in Special Issue
A High-Throughput Assay for Congenital and Age-Related Eye Diseases in Zebrafish
Article Menu
Issue 2 (June) cover image

Export Article

Open AccessArticle

The Glycogen Synthase Kinase-3β Inhibitor LSN 2105786 Promotes Zebrafish Fin Regeneration

Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
Lilly Research Laboratories, Indianapolis, IN 46225, USA
Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA
Molecular Templates, Austin, TX 78729, USA
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(2), 30;
Received: 22 March 2019 / Revised: 12 April 2019 / Accepted: 14 April 2019 / Published: 19 April 2019
(This article belongs to the Special Issue Zebrafish Models for Development and Disease)
PDF [3566 KB, uploaded 19 April 2019]


The Wnt pathway has been shown to regulate bone homeostasis and to influence some bone disease states. We utilized a zebrafish model system to study the effects of a synthetic, orally bioavailable glycogen synthase kinase-3β (GSK3β) inhibitor LSN 2105786, which activates Wnt signaling during bone healing and embryogenesis. GSK3β inhibitor treatment was used to phenocopy GSK3β morpholino oligonucleotide (MO) knockdown in zebrafish embryos. Human and zebrafish synthetic mRNA injection were similarly effective at rescue of GSK3β MO knockdown. During caudal fin regeneration, bony rays are the first structure to differentiate in zebrafish fins, providing a useful model to study bone healing. Caudal fin regeneration experiments were conducted using various concentrations of a GSK3β inhibitor, examining duration and concentration dependence on regenerative outgrowth. Experiments revealed continuous low concentration (4–5 nM) treatment to be more effective at increasing regeneration than intermittent dosing. Higher concentrations inhibited fin growth, perhaps by excessive stimulation of differentiation programs. Increased Wnt responsive gene expression and differentiation were observed in response to GSK3b inhibitor treatment. Activating Wnt signaling also increased cell proliferation and osteoblast differentiation in fin regenerates. Together, these data indicate that bone healing in zebrafish fin regeneration was improved by activating Wnt signaling using GSK3b inhibitor treatment. In addition, caudal fin regeneration is useful to evaluate dose-dependent pharmacological efficacy in bone healing, various dosing regimens and possible toxicological effects of compounds. View Full-Text
Keywords: zebrafish; glycogen synthase kinase-3β; bone healing; regeneration; caudal fin zebrafish; glycogen synthase kinase-3β; bone healing; regeneration; caudal fin

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Sarmah, S.; Curtis, C.; Mahin, J.; Farrell, M.; Engler, T.A.; Sanchez-Felix, M.V.; Sato, M.; Ma, Y.L.; Chu, S.; Marrs, J.A. The Glycogen Synthase Kinase-3β Inhibitor LSN 2105786 Promotes Zebrafish Fin Regeneration. Biomedicines 2019, 7, 30.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Biomedicines EISSN 2227-9059 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top