Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone.

Original languageEnglish (US)
Article numbere17772
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - 2011

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Dinoprostone
prostaglandins
Bone
Wnt Signaling Pathway
bones
Osteoblasts
Bone and Bones
osteoblasts
Mutation
receptors
antagonists
Prostaglandin Receptors
Catenins
mutation
Osteoclasts
osteoclasts
Cyclic AMP
Bone Density
Small Interfering RNA
cyclic AMP

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Prostaglandin E2 signals through PTGER2 to regulate sclerostin expression. / Genetos, Damian C; Yellowley-genetos, Clare E; Loots, Gabriela G.

In: PLoS One, Vol. 6, No. 3, e17772, 2011.

Research output: Contribution to journalArticle

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