title: The protective role of the pericellular matrix in chondrocyte apoptosis.
abstract: BACKGROUND
  This study was designed to quantify the role of the pericellular matrix (PCM) in chondrocyte apoptosis using chondrons, which are a cartilage functional unit including a chondrocyte and its associated PCM.
  
  
  METHODS
  Chondrocytes and chondrons were enzymatically isolated from human articular cartilage and exposed to monosodium iodoacetate (MIA) and staurosporine for apoptosis induction. Chondrons were defined by the presence of type VI collagen, a basic component of the PCM. Apoptosis of chondrocytes and chondrons was measured with annexin V binding by flow cytometry and verified with terminal dUTP nick end-labeling staining. In a separate experiment, isolated chondrocytes were treated with soluble type VI collagen, before or after apoptosis induction with MIA, and cell death was measured by the activity of LDH and terminal dUTP nick end-labeling staining.
  
  
  RESULTS
  Chondrocytes treated with MIA incurred 27% cell death, compared with 12% in chondrons. On treating with MIA, 9% of chondrocytes underwent apoptosis, compared with only 1.6% of chondrons. Similarly, staurosporine induced 13% apoptosis in chondrocytes, whereas it was 3% in chondrons. Preincubation of type VI collagen effectively prevented chondrocytes from MIA-induced cell death. After apoptosis was induced with MIA, however, treatment with type VI collagen failed to rescue chondrocytes from death.
  
  
  CONCLUSIONS
  The PCM, a native microenvironment of chondrocytes, protects chondrocytes from apoptosis. Type VI collagen is a functional component of the PCM that contributes to the survival of chondrocytes.
authors: Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, Missouri 63110, USA.
authors: H Charlie
authors: HC
authors: Peters
authors: Thomas J
authors: TJ
authors: Otto
authors: J Tyler
authors: JT
authors: Enders
authors: Wu
authors: W
authors: Jin
authors: Berton R
authors: BR
authors: Moed
authors: Zijun
authors: Z
authors: Zhang
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D024142:Collagen Type VI / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007461:Iodoacetates / Q000494:pharmacology; D020011:Protective Agents / Q000378:metabolism*; D012995:Solubility / Q000187:drug effects; D013194:Staining and Labeling; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D024142:Collagen Type VI; D007461:Iodoacetates; D020011:Protective Agents; D019311:Staurosporine