Under-sulfation by PAPS synthetase inhibition modulates the expression of ECM molecules during chondrogenesis

Young Rae Cho, Sun Joo Lee, Hong Bae Jeon, Zee Yong Park, Jang Soo Chun, Yung Joon Yoo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Sulfation of proteoglycans is an important post-translational modification in chondrocytes. We previously found that 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthetase-2 levels increased more than 10-fold during mesenchymal cell chondrogenesis. Given that PAPS is the sole sulfur donor, and is produced only by PAPS synthetase in all cells, increased expression of PAPS synthetase-2 should be a prerequisite for increased sulfation activity of chondrocytes. We found that sodium chlorate, a specific inhibitor of PAPS synthetase, inhibited proteoglycan sulfation during chondrogenesis. In contrast, sodium chlorate unexpectedly induced early expression of type II collagen and increased the number of cartilage nodules during chondrogenesis. Inhibition of sulfation also accelerated the down-regulation of N-cadherin and fibronectin during chondrogenesis. These findings suggest that sulfation has an important regulatory role in coordinating the timely expression of extracellular matrix molecules during chondrogenesis, and that under-sulfation may cause the breakdown of this coordination, leading to premature chondrogenesis.

Original languageEnglish
Pages (from-to)769-775
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number3
DOIs
StatePublished - Oct 22 2004

Keywords

  • Chondrogenesis
  • Extracellular matrix
  • Fibronectin
  • N-cadherin
  • PAPS synthetase
  • Sodium chlorate
  • Sulfation
  • Type II collagen

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