title: Under-sulfation by PAPS synthetase inhibition modulates the expression of ECM molecules during chondrogenesis.
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.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Cho
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hong Bae
authors.initials: HB
authors.lastname: Jeon
authors.forename: Zee Yong
authors.initials: ZY
authors.lastname: Park
authors.forename: Jang-Soo
authors.initials: JS
authors.lastname: Chun
authors.forename: Yung Joon
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: 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*
chemical_list: 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