Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway

Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway

Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pa...

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Main Authors: Fong, Gloria, Backman, Ludvig J., Andersson, Gustav, Scott, Alexander, Danielson, Patrik
Format: Online
Language:English
Published: Springer-Verlag 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582816/
id pubmed-3582816
recordtype oai_dc
spelling pubmed-35828162013-02-27 Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway Fong, Gloria Backman, Ludvig J. Andersson, Gustav Scott, Alexander Danielson, Patrik Regular Article Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue. Springer-Verlag 2012-12-05 2013-03 /pmc/articles/PMC3582816/ /pubmed/23212463 http://dx.doi.org/10.1007/s00441-012-1530-5 Text en © The Author(s) 2012 Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fong, Gloria
Backman, Ludvig J.
Andersson, Gustav
Scott, Alexander
Danielson, Patrik
spellingShingle Fong, Gloria
Backman, Ludvig J.
Andersson, Gustav
Scott, Alexander
Danielson, Patrik
Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
author_facet Fong, Gloria
Backman, Ludvig J.
Andersson, Gustav
Scott, Alexander
Danielson, Patrik
author_sort Fong, Gloria
title Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
title_short Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
title_full Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
title_fullStr Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
title_full_unstemmed Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway
title_sort human tenocytes are stimulated to proliferate by acetylcholine through an egfr signalling pathway
description Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue.
publisher Springer-Verlag
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582816/
_version_ 1611957717889449984

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