Proteomics Perspectives in Rotator Cuff Research: A Systematic Review of Gene Expression and Protein Composition in Human Tendinopathy

<div><p>Background</p><p>Rotator cuff tendinopathy including tears is a cause of significant morbidity. The molecular pathogenesis of the disorder is largely unknown. This review aimed to present an overview of the literature on gene expression and protein composition in human rotator cuff tendinopathy and other tendinopathies, and to evaluate perspectives of proteomics – the comprehensive study of protein composition - in tendon research.</p><p>Materials and Methods</p><p>We conducted a systematic search of the literature published between 1 January 1990 and 18 December 2012 in PubMed, Embase, and Web of Science. We included studies on objectively quantified differential gene expression and/or protein composition in human rotator cuff tendinopathy and other tendinopathies as compared to control tissue.</p><p>Results</p><p>We identified 2199 studies, of which 54 were included; 25 studies focussed on rotator cuff or biceps tendinopathy. Most of the included studies quantified prespecified mRNA molecules and proteins using polymerase chain reactions and immunoassays, respectively. There was a tendency towards an increase of collagen I (11 of 15 studies) and III (13 of 14), metalloproteinase (MMP)-1 (6 of 12), -9 (7 of 7), -13 (4 of 7), tissue inhibitor of metalloproteinase (TIMP)-1 (4 of 7), and vascular endothelial growth factor (4 of 7), and a decrease in MMP-3 (10 of 12). Fourteen proteomics studies of tendon tissues/cells failed inclusion, mostly because they were conducted in animals or in vitro.</p><p>Conclusions</p><p>Based on methods, which only allowed simultaneous quantification of a limited number of prespecified mRNA molecules or proteins, several proteins appeared to be differentially expressed/represented in rotator cuff tendinopathy and other tendinopathies. No proteomics studies fulfilled our inclusion criteria, although proteomics technologies may be a way to identify protein profiles (including non-prespecified proteins) that characterise specific tendon disorders or stages of tendinopathy. Thus, our results suggested an untapped potential for proteomics in tendon research.</p></div

Experimental techniques used for the analysis of gene expression and protein composition.

<p>Abbreviations: RT-PCR = reverse transcription polymerase chain reaction, RNA-seq = RNA sequencing, ELISA = enzyme-linked immunosorbent assay.</p><p>Experimental techniques used for the analysis of gene expression and protein composition.</p

Flow diagram showing the inclusion process.

<p>Flow diagram showing the inclusion process.</p

Direction of change of matrix metalloproteinase 3 (MMP-3) in relation to study size (number of patient samples).

<p>Each dot marks the direction of change in MMP-3 in a single study[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref033" target="_blank">33</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref040" target="_blank">40</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref042" target="_blank">42</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref045" target="_blank">45</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref050" target="_blank">50</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref059" target="_blank">59</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref066" target="_blank">66</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref067" target="_blank">67</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref073" target="_blank">73</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref078" target="_blank">78</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119974#pone.0119974.ref086" target="_blank">86</a>].</p