Prostaglandin expression profile in hypoxic osteoblastic cells

Christina M. Lee, Damian C Genetos, Alice Wong, Clare E Yellowley-genetos

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Conditions such as fracture and unloading have been shown to be associated with tissue and cellular hypoxia in bone. The effects of hypoxia on bone cell physiology and ultimately its impact on bone tissue repair and remodeling are not well understood. In this study, we investigated the role of hypoxia on prostaglandin release from osteoblastic cells cultured in 2% (hypoxia), 5% (potentially cellular normoxia), and 21% (normoxia for standard cell culture conditions) oxygen for up to 24 h. We quantified the effects of reduced oxygen tension on the release of prostaglandin (PG)E2, PGF , PGD2, and PGI2. The mechanism by which hypoxia increases PG production was investigated by examining the various regulatory components of the PG biosynthetic pathway. Our data show that PGE2 levels alone are significantly elevated under hypoxic conditions. Also, we show that cyclooxygenase (COX)-1 and COX-2 play an important role in hypoxia-induced PGE2 production, possibly via a mechanism involving changes in their respective activity levels under low oxygen conditions. The effect of hypoxia on PGE2 levels was mimicked by dimethyloxaloglycine, a known activator of the HIF pathway. In addition, we confirmed that HIF-1α was stabilized in osteoblastic cells under hypoxia. Taken together these data suggest a role for the HIF pathway in regulation of PGE2 levels under hypoxic conditions. Previous studies have detected release of prostaglandins from areas of damaged bone, such as a fracture site, and our data may contribute to an understanding of how this release is regulated.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalJournal of Bone and Mineral Metabolism
Volume28
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Bone
  • Cyclooxygenase
  • Hypoxia
  • Osteoblastic cells
  • Prostaglandins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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