Apoptosis staining in cultured pseudoachondroplasia chondrocytes

Jackie Duke, D. Montufar-Solis, S. Underwood, Zahid S. Lalani, J. T. Hecht

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Pseudoachondroplasia (PSACH) is a skeletal dysplasia caused by a mutation in cartilage oligomeric matrix protein (COMP), a glycoprotein of normal cartilage matrix. PSACH chondrocytes have a distinctive phenotype with enlarged rER cisternae containing COMP, aggrecan, type IX collagen, and chaperone proteins. Ultrastructural studies suggested that this accumulation compromises cell function, hastening cell death, and consequently reducing the number of cells in the growth plate contributing to linear bone growth. Using the alginate bead system, we cultured control and PSACH chondrocytes for twenty weeks and one year to determine the effect of the mutation on size and number of cartilage nodules; and the presence of apoptotic cell death (TUNEL assay). At 20 weeks, beads containing PSACH or control chondrocytes did not differ in size and number of cartilage nodules or number of TUNEL-positive cells. After one year, nodule number, size and percent cartilage per bead were significantly less in PSACH nodules, and the number of cells staining positive for apoptosis was significantly greater than in controls (71.8% vs. 44.6%). The increase in apoptosis in PSACH nodules correlates with a decrease in growth of cartilage, supporting our hypothesis that death of damaged cells contributes to the growth plate defects in PSACH.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalApoptosis
Volume8
Issue number2
DOIs
StatePublished - Mar 2003

Keywords

  • Apoptosis
  • Chondrocytes
  • Chondrodysplasia
  • COMP
  • Pseudoachondroplasia cartilage

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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