title: Local biochemical and morphological differences in human Achilles tendinopathy: a case control study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN20896880.
authors.affiliation: 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. jessica.pingel@gmx.de
authors.forename: Pingel
authors.initials: P
authors.lastname: J
authors.forename: Fredberg
authors.initials: F
authors.lastname: U
authors.forename: Qvortrup
authors.initials: Q
authors.lastname: K
authors.forename: Larsen
authors.initials: L
authors.lastname: J O
authors.forename: Schjerling
authors.initials: S
authors.lastname: P
authors.forename: Heinemeier
authors.initials: H
authors.lastname: K
authors.forename: Kjaer
authors.initials: K
authors.lastname: M
authors.forename: Langberg
authors.initials: L
authors.lastname: H
mesh_terms: D000125:Achilles Tendon / Q000737:chemistry* / Q000473:pathology* / Q000648:ultrastructure; D001706:Biopsy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002908:Chronic Disease; D017364:Collagenases / Q000235:genetics; D003718:Denmark; D024022:Fibrillar Collagens / Q000235:genetics / Q000648:ultrastructure; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D052256:Tendinopathy / Q000235:genetics* / Q000473:pathology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics
chemical_list: D024022:Fibrillar Collagens; D005819:Genetic Markers; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases