Tendinopathy and tears of the rotator cuff are associated with hypoxia and apoptosis

J Bone Joint Surg Br. 2010 Mar;92(3):448-53. doi: 10.1302/0301-620X.92B3.23074.


The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff. We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1alpha (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1alpha regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis). The HIF-1alpha expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears. These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis
  • Cell Hypoxia
  • DNA Fragmentation
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Proto-Oncogene Proteins / metabolism
  • Rotator Cuff / metabolism
  • Rotator Cuff / pathology
  • Rotator Cuff Injuries*
  • Shoulder Impingement Syndrome / metabolism
  • Shoulder Impingement Syndrome / pathology*
  • Tendinopathy / metabolism
  • Tendinopathy / pathology*
  • Young Adult


  • BNIP3 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • Proto-Oncogene Proteins