Under-sulfation by PAPS synthetase inhibition modulates the expression of ECM molecules during chondrogenesis.
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.
Cho
Young Rae
YR
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Lee
Sun Joo
SJ
Jeon
Hong Bae
HB
Park
Zee Yong
ZY
Chun
Jang-Soo
JS
Yoo
Yung Joon
YJ
D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D002645:Chickens; D002704:Chlorates / Q000494:pharmacology; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D024043:Collagen Type II; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D013430:Sulfate Adenylyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*
D002704:Chlorates; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D009097:Multienzyme Complexes; D011509:Proteoglycans; D013431:Sulfates; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase; C032706:sodium chlorate