title: Gene expression profiles of changes underlying different-sized human rotator cuff tendon tears.
abstract: BACKGROUND
  Progressive cellular and extracellular matrix (ECM) changes related to age and disease severity have been demonstrated in rotator cuff tendon tears. Larger rotator cuff tears demonstrate structural abnormalities that potentially adversely influence healing potential. This study aimed to gain greater insight into the relationship of pathologic changes to tear size by analyzing gene expression profiles from normal rotator cuff tendons, small rotator cuff tears, and large rotator cuff tears.
  
  
  METHODS
  We analyzed gene expression profiles of 28 human rotator cuff tendons using microarrays representing the entire genome; 11 large and 5 small torn rotator cuff tendon specimens were obtained intraoperatively from tear edges, which we compared with 12 age-matched normal controls. We performed real-time polymerase chain reaction and immunohistochemistry for validation.
  
  
  RESULTS
  Torn rotator cuff tendons demonstrated upregulation of a number of key genes, such as matrix metalloproteinase 3, 10, 12, 13, 15, 21, and 25; a disintegrin and metalloproteinase (ADAM) 12, 15, and 22; and aggrecan. Amyloid was downregulated in all tears. Small tears displayed upregulation of bone morphogenetic protein 5. Chemokines and cytokines that may play a role in chemotaxis were altered; interleukins 3, 10, 13, and 15 were upregulated in tears, whereas interleukins 1, 8, 11, 18, and 27 were downregulated.
  
  
  CONCLUSIONS
  The gene expression profiles of normal controls and small and large rotator cuff tear groups differ significantly. Extracellular matrix remodeling genes were found to contribute to rotator cuff tear pathogenesis. Rotator cuff tears displayed upregulation of a number of matrix metalloproteinase (3, 10, 12, 13, 15, 21, and 25), a disintegrin and metalloproteinase (ADAM 12, 15, and 22) genes, and downregulation of some interleukins (1, 8, and 27), which play important roles in chemotaxis. These gene products may potentially have a role as biomarkers of failure of healing or therapeutic targets to improve tendon healing.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Surgery, Nuffield Orthopaedic Center, University of Oxford, Oxford, UK. Electronic address: salmachaudhury@doctors.org.uk.
authors.forename: Salma
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: University of Swansea, Swansea, UK.
authors.forename: Zhidao
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Surgery, Nuffield Orthopaedic Center, University of Oxford, Oxford, UK.
authors.forename: Dipti
authors.initials: D
authors.lastname: Thakkar
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Surgery, Nuffield Orthopaedic Center, University of Oxford, Oxford, UK.
authors.forename: Osnat
authors.initials: O
authors.lastname: Hakimi
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Surgery, Nuffield Orthopaedic Center, University of Oxford, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carr
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D025341:Principal Component Analysis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D000070636:Rotator Cuff Injuries / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D007378:Interleukins; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases
keywords: Rotator cuff tear; extracellular matrix (ECM); gene expression; immunohistochemistry; matrix metalloproteinase (MMPs); microarray