PMID- 25743255 OWN - NLM STAT- MEDLINE DCOM- 20160128 LR - 20181113 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 294 DP - 2015 May 21 TI - Activation of the Wnt/beta-catenin signaling cascade after traumatic nerve injury. PG - 101-8 LID - S0306-4522(15)00208-0 [pii] LID - 10.1016/j.neuroscience.2015.02.049 [doi] AB - Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via beta-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and beta-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and beta-catenin levels. Moreover, a novel Wnt/beta-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2 weeks post-injury and remained upregulated for 2 months. Additionally, beta-catenin was activated at 2 months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef:H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/beta-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury. CI - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Kurimoto, S AU - Kurimoto S AD - Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA; Department of Hand Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya 466-8550, Japan. FAU - Jung, J AU - Jung J AD - Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA. FAU - Tapadia, M AU - Tapadia M AD - Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA. FAU - Lengfeld, J AU - Lengfeld J AD - Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA. FAU - Agalliu, D AU - Agalliu D AD - Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA. FAU - Waterman, M AU - Waterman M AD - Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697, USA. FAU - Mozaffar, T AU - Mozaffar T AD - Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA; Department of Neurology, University of California, Irvine, CA 92697, USA. FAU - Gupta, R AU - Gupta R AD - Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA; Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USA. Electronic address: ranjang@uci.edu. LA - eng GR - R01 HL116995/HL/NHLBI NIH HHS/United States GR - R01 NS049203/NS/NINDS NIH HHS/United States GR - 2R01NS049203-06A1/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150303 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (CTNNB1 protein, mouse) RN - 0 (Receptors, Cholinergic) RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) SB - IM MH - Animals MH - Cell Line MH - Male MH - Mice, 129 Strain MH - Mice, Transgenic MH - *Muscle Denervation/methods MH - Neuromuscular Junction/*injuries/metabolism MH - Receptors, Cholinergic/metabolism MH - Wnt Proteins/*metabolism MH - *Wnt Signaling Pathway/physiology MH - beta Catenin/*metabolism PMC - PMC5384639 MID - NIHMS853816 OTO - NOTNLM OT - Wnt signaling OT - neuromuscular junction OT - peripheral nerve OT - traumatic nerve injury EDAT- 2015/03/07 06:00 MHDA- 2016/01/29 06:00 PMCR- 2017/04/07 CRDT- 2015/03/07 06:00 PHST- 2014/12/20 00:00 [received] PHST- 2015/02/24 00:00 [revised] PHST- 2015/02/25 00:00 [accepted] PHST- 2015/03/07 06:00 [entrez] PHST- 2015/03/07 06:00 [pubmed] PHST- 2016/01/29 06:00 [medline] PHST- 2017/04/07 00:00 [pmc-release] AID - S0306-4522(15)00208-0 [pii] AID - 10.1016/j.neuroscience.2015.02.049 [doi] PST - ppublish SO - Neuroscience. 2015 May 21;294:101-8. doi: 10.1016/j.neuroscience.2015.02.049. Epub 2015 Mar 3.