Document Detail

Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway.
MedLine Citation:
PMID:  23212463     Owner:  NLM     Status:  MEDLINE    
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.
Gloria Fong; Ludvig J Backman; Gustav Andersson; Alexander Scott; Patrik Danielson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-05
Journal Detail:
Title:  Cell and tissue research     Volume:  351     ISSN:  1432-0878     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-27     Completed Date:  2013-08-07     Revised Date:  2014-03-10    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  465-75     Citation Subset:  IM    
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MeSH Terms
Acetylcholine / pharmacology*
Achilles Tendon / cytology*
Blotting, Western
Bromodeoxyuridine / metabolism
Cell Proliferation / drug effects
Cell Survival / drug effects
Cells, Cultured
Choline O-Acetyltransferase / metabolism
Models, Biological
Phosphorylation / drug effects
Polymerase Chain Reaction
Receptor, Epidermal Growth Factor / metabolism*
Receptors, Muscarinic / metabolism
Signal Transduction / drug effects*
Vesicular Acetylcholine Transport Proteins / metabolism
Grant Support
126604-1//Canadian Institutes of Health Research
Reg. No./Substance:
0/Receptors, Muscarinic; 0/Vesicular Acetylcholine Transport Proteins; EC O-Acetyltransferase; EC, Epidermal Growth Factor; G34N38R2N1/Bromodeoxyuridine; N9YNS0M02X/Acetylcholine

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