SOX9 expression does not correlate with type II collagen expression in adult articular chondrocytes

Thomas Aigner, Pia Margarethe Gebhard, Erik Schmid, Brigitte Bau, Vincent Harley, Ernst Pöschl

Research output: Contribution to journalArticleResearchpeer-review

127 Citations (Scopus)

Abstract

Anabolic activity is a crucial activity of articular chondrocytes and its failure is one major reason of osteoarthritic cartilage degeneration. The intracellular factors responsible for the increase or decrease of anabolic activity of articular chondrocytes remain largely unknown. A recent candidate, the transcription factor SOX9, has elicited much interest as it is suggested to be a central factor in chondrocytic differentiation during development, including collagen type II (COL2A1) expression, the major anabolic gene product of chondrocytes. Here we show that normal adult human articular chondrocytes in vivo contain high SOX9 mRNA levels, which are decreased in osteoarthritic cartilage. Surprisingly, no positive correlation between SOX9 and COL2A1 expression was observed - to the contrary, the expression of COL2A1 was significantly increased in the diseased cells. Immunolocalization confirmed the presence of SOX9 protein in normal and osteoarthritic chondrocytes without showing significant differences in both SOX9 quantity and subcellular localization in osteoarthritic compared to normal cartilage tissue. Interestingly, laser scanning confocal microscopy showed that the subcellular distribution of SOX9 in adult chondrocytes was not restricted to the nucleus as observed in fetal chondrocytes, but was also detected within the cytoplasm, with no differences in subcellular SOX9 distribution between normal and OA cartilage. This is consistent with the lack of positive correlation between SOX9 and COL2A1 expression in adult articular chondrocytes. Also, no positive correlation between SOX9 and COL2A1 expression was observed in vitro after challenge of chondrocytes with Il-1β, which is a strong (negative) regulator of COL2A1 expression, or with IGF-I, which stimulates COL2A1 expression. These results suggest that SOX9 is not the key regulator of COL2A1 promoter activity in human adult articular chondrocytes. However, SOX9 might still be involved in maintaining the chondrocytic phenotype in normal and osteoarthritic cartilage.

Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalMatrix Biology
Volume22
Issue number4
DOIs
Publication statusPublished - 1 Jan 2003
Externally publishedYes

Keywords

  • Aggrecan
  • Cartilage
  • Collagen
  • Osteoarthritis
  • SOX9

Cite this