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Open Access Highly Accessed Research article

Local biochemical and morphological differences in human Achilles tendinopathy: a case control study

Pingel J1*, Fredberg U2, Qvortrup K3, Larsen JO4, Schjerling P1, Heinemeier K1, Kjaer M1 and Langberg H5

Author Affiliations

1 Institute of Sports Medicine, Department of Orthopedic Surgery M. Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

2 Department of Rheumatology, Silkeborg Hospital, Silkeborg, Denmark

3 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

4 Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

5 Department of Public Health, University of Copenhagen, Copenhagen, Denmark

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BMC Musculoskeletal Disorders 2012, 13:53  doi:10.1186/1471-2474-13-53

Published: 5 April 2012



The incidence of Achilles tendinopathy is high and underlying etiology as well as biochemical and morphological pathology associated with the disease is largely unknown. The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The expressions of growth factors, inflammatory mediators and tendon morphology were determined in both chronically diseased and healthy tendon parts.


Thirty Achilles tendinopathy patients were randomized to an expression-study (n = 16) or a structural-study (n = 14). Biopsies from two areas in the Achilles tendon were taken and structural parameters: fibril density, fibril size, volume fraction of cells and the nucleus/cytoplasm ratio of cells were determined. Further gene expressions of various genes were analyzed.


Significantly smaller collagen fibrils and a higher volume fraction of cells were observed in the tendinopathic region of the tendon. Markers for collagen and its synthesis collagen 1, collagen 3, fibronectin, tenascin-c, transforming growth factor-β fibromodulin, and markers of collagen breakdown matrix metalloproteinase-2, matrix metalloproteinase-9 and metallopeptidase inhibitor-2 were significantly increased in the tendinopathic region. No altered expressions of markers for fibrillogenesis, inflammation or wound healing were observed.


The present study indicates that an increased expression of factors stimulating the turnover of connective tissue is present in the diseased part of tendinopathic tendons, associated with an increased number of cells in the injured area as well as an increased number of smaller and thinner fibrils in the diseased tendon region. As no fibrillogenesis, inflammation or wound healing could be detected, the present data supports the notion that tendinopathy is an ongoing degenerative process.

Trial registration

Current Controlled Trials ISRCTN20896880

Collagen; Gene expression; Patients; Growth factors; Tissue turnover