Shear-induced cyclooxygenase-2 via a JNK2/c-Jun-dependent pathway regulates prostaglandin receptor expression in chondrocytic cells

James P. Abulencia, Renee Gaspard, Zachary R. Healy, William A. Gaarde, John Quackenbush, Konstantinos Konstantopoulos

Research output: Contribution to journalArticle

Abstract

Using cDNA microarrays coupled with bioinformatics tools, we elucidated a signaling cascade regulating cyclooxygenase-2 (COX-2), a pivotal pro-inflammatory enzyme expressed in rheumatic and osteoarthritic, but not normal, cartilage. Exposure of T/C-28a2 chondrocytic cells to fluid shear results in co-regulation of c-Jun N-terminal kinase2 (JNK2), c-Jun, and COX-2 as well as concomitant downstream expression of prostaglandin receptors EP2 and EP3a1. JNK2 transcript inhibition abrogated shear-induced COX-2, EP2, and EP3a1 mRNA up-regulation as well as c-Jun phosphorylation. Functional knock-out experiments using an antisense c-Jun oligonucleotide revealed the abolition of shear-induced COX-2, EP2, and EP3a1, but not JNK2, transcripts. Moreover, inhibition of COX-2 activity eliminated mRNA upregulation of EP2 and EP3a1 induced by shear. Hence, a biochemical pathway exists wherein fluid shear activates COX-2, via a JNK2/c-Jun-dependent pathway, which in turn elicits downstream EP2 and EP3a1 mRNA synthesis.

Original languageEnglish (US)
Pages (from-to)28388-28394
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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