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Protein differences between human trapezius and vastus lateralis muscles determined with a proteomic approach
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
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2011 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, Vol. 12, no 181, 11- p.Article in journal (Refereed) Published
Abstract [en]

Background: The trapezius muscle is a neck muscle that is susceptible to chronic pain conditions associated with repetitive tasks, commonly referred to as chronic work-related myalgia, hence making the trapezius a muscle of clinical interest. To provide a basis for further investigations of the proteomic traits of the trapezius muscle in disease, two-dimensional difference gel electrophoresis (2D-DIGE) was performed on the healthy trapezius using vastus lateralis as a reference. To obtain as much information as possible from the vast proteomic data set, both one-way ANOVA, with and without false discovery rate (FDR) correlation, and partial least square projection to latent structures with discriminant analysis (PLS-DA) were combined to compare the outcome of the analysis.

Results: The trapezius and vastus lateralis showed significant differences in metabolic, contractile and regulatory proteins, with different results depending on choice of statistical approach and pre-processing technique. Using the standard method, FDR correlated one-way ANOVA, 42 protein spots differed significantly in abundance between the two muscles. Complementary analysis using immunohistochemistry and western blot confirmed the results from the 2D-DIGE analysis.

Conclusions: The proteomic approach used in the present study combining 2D-DIGE and multivariate modelling provided a more comprehensive comparison of the protein profiles of the human trapezius and vastus lateralis muscle, than previously possible to obtain with immunohistochemistry or SDS-PAGE alone. Although 2D-DIGE has inherent limitations it is particularly useful to comprehensively screen for important structural and metabolic proteins, and appears to be a promising tool for future studies of patients suffering from chronic work related myalgia or other muscle diseases.

Place, publisher, year, edition, pages
BioMed Central , 2011. Vol. 12, no 181, 11- p.
National Category
Basic Medicine
URN: urn:nbn:se:umu:diva-46108DOI: 10.1186/1471-2474-12-181PubMedID: 21831281OAI: diva2:437017
Available from: 2011-08-26 Created: 2011-08-26 Last updated: 2013-12-12Bibliographically approved
In thesis
1. Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia
Open this publication in new window or tab >>Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[en]
Tillämpning av proteomiska och metabolomiska metoder på human skelettmuskel med inriktning mot kronisk trapezius myalgi
Abstract [en]

Work related musculoskeletal disorders are the dominating causes of reported ill-health in industrialized countries. These chronic pain conditions are one of the most costly public health problems in Europe and North America. When work related musculoskeletal disorders are considered to be of muscular origin and the trapezius muscle is affected, the common appellation is trapezius myalgia. Since little is known about the genesis or how it is maintained, it is of great importance to better understand the pathophysiology of trapezius myalgia; doing so will better enable recommendations for prevention, treatment and rehabilitation. Several hypotheses have been presented based on biochemical alterations in the muscle, suggesting increased signaling of inflammatory substances and altered metabolism. Previous research has not been able to present the comprehensive picture of the muscle in pain. Thus there is a demand for more comprehensive research regarding the biochemical milleu of the chronic trapezius muscle.

Proteomic and metabolomic methods allow non-targeted simultaneous analyses of a large number of proteins and metabolites. The main emphasis in this thesis is on a proteomic method, two-dimensional differential gel electrophoresis (2D-DIGE). The method is validated to human skeletal muscle biopsy research with laboratory specific settings. In the baseline study, there were 14 metabolic, contractile, structural and regulatory proteins that differed significantly in abundance when trapezius and vastus lateralis muscles were compared. Using the validated 2D-DIGE method and the baseline study, a comparison between healthy and myalgic muscles was made. Biopsies from female cleaners with and without myalgia were compared to obtain results from women with the same type of work exposure. In the multivariate model, 28 identified unique proteins separated healthy and myalgic muscle and were grouped according to function: metabolic (n=10), contractile (n=9), regulatory (n=3), structural (n=4), and other (n=2). Finally, a second screening method, metabolomics, was introduced to analyze differences in metabolite content as a complement to and verification of the proteomic results. Gas chromatography-mass spectrometry (GC-MS) was performed on muscle interstitial fluid samples obtained with microdialysis, and differences in the abundance of extracellular metabolites were revealed.

 The 2D-DIGE method is a reliable method to analyze human skeletal muscle. The outcomes of the proteomic analyses were dependant on the statistical approach. Systematic differences in protein and metabolite content were detected using a multivariate approach. Univariate analyses were used to analyze individual proteins for their significance. The significant proteins in the baseline study were predominately related to muscle fiber type which correlated with the differences in fiber type content between trapezius and vastus lateralis. The proteomic and metabolomics studies where myalgic and healthy muscles were compared provide us with new clues and new aspects regarding the pathophysiology of the myalgic muscle.

Technically advanced methods employed in the thesis enabled an explorative screening of proteins of relevance for the pathophysiology of the myalgic muscle. The results of these analyses may contribute to the formulation of future hypothesis that need to be further evaluated.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2012. 60 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1533
Trapezius myalgia, proteomics, 2D-DIGE, metabolomics, microdialysate, biopsies
National Category
Other Basic Medicine
Research subject
Human Anatomy
urn:nbn:se:umu:diva-61399 (URN)978-91-7459-515-4 (ISBN)
Public defence
2012-12-06, BiA 201, Biologihuset, Umeå Universitet, Umeå, 09:00 (English)
Available from: 2012-11-15 Created: 2012-11-12 Last updated: 2012-11-15Bibliographically approved

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Hadrevi, JennyHellström, FredrikKieselbach, ThomasMalm, ChristerPedrosa-Domellöf, Fatima
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