title: Ionizing radiation causes active degradation and reduces matrix synthesis in articular cartilage.
abstract: OBJECTIVE
  Little is known regarding radiation effects on adult articular (joint) cartilage, though joint damage has been reported following cancer treatment or occupational exposures. The aim of this study was to determine if radiation can reduce cartilage matrix production, induce cartilage degradation, or interfere with the anabolic effects of IGF-1.
  
  
  METHODS
  Isolated chondrocytes cultured in monolayers and whole explants harvested from ankles of human donors and knees of pigs were irradiated with 2 or 10 Gy γ-rays, with or without IGF-1 stimulation. Proteoglycan synthesis and IGF-1 signaling were examined at Day 1; cartilage degradation throughout the first 96 hours.
  
  
  RESULTS
  Human and pig cartilage responded similarly to radiation. Cell viability was unchanged. Basal and IGF-1 stimulated proteoglycan synthesis was reduced following exposure, particularly following 10 Gy. Both doses decreased IGF-induced Akt activation and IGF-1 receptor phosphorylation. Matrix metalloproteinases (ADAMTS5, MMP-1, and MMP-13) and proteoglycans were released into media after 2 and 10 Gy.
  
  
  CONCLUSIONS
  Radiation induced an active degradation of cartilage, reduced proteoglycan synthesis, and impaired IGF-1 signaling in human and pig chondrocytes. Lowered Akt activation could account for decreased matrix synthesis. Radiation may cause a functional decline of cartilage health in joints after exposure, contributing to arthropathy.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA. jwilley@wakehealth.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Willey
authors.forename: David L
authors.initials: DL
authors.lastname: Long
authors.forename: Kadie S
authors.initials: KS
authors.lastname: Vanderman
authors.forename: Richard F
authors.initials: RF
authors.lastname: Loeser
mesh_terms: D000328:Adult; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D013552:Swine
chemical_list: D006025:Glycosaminoglycans; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; D004247:DNA