Loading-related regulation of transcription factor EGR2/Krox-20 in bone cells is ERK1/2 protein-mediated and prostaglandin, Wnt signaling pathway-, and insulin-like growth factor-I axis-dependent

Gul Zaman, Andrew Sunters, Gabriel L Galea, Behzad Javaheri, Leanne K Saxon, Alaa Moustafa, Victoria J Armstrong, Joanna S Price, Lance E Lanyon

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)

Abstract

Of the 1,328 genes revealed by microarray to be differentially regulated by disuse, or at 8 h following a single short period of osteogenic loading of the mouse tibia, analysis by predicting associated transcription factors from annotated affinities revealed the transcription factor EGR2/Krox-20 as being more closely associated with more pathways and functions than any other. Real time quantitative PCR confirmed up-regulation of Egr2 mRNA expression by loading of the tibia in vivo. In vitro studies where strain was applied to primary cultures of mouse tibia-derived osteoblastic cells and the osteoblast UMR106 cell line also showed up-regulation of Egr2 mRNA expression. In UMR106 cells, inhibition of β1/β3 integrin function had no effect on strain-related Egr2 expression, but it was inhibited by a COX2-selective antagonist and imitated by exogenous prostaglandin E2 (PGE2). This response to PGE(2) was mediated chiefly through the EP1 receptor and involved stimulation of PKC and attenuation by cAMP/PKA. Neither activators nor inhibitors of nitric oxide, estrogen signaling, or LiCl had any effect on Egr2 mRNA expression, but it was increased by both insulin-like growth factor-1 and high, but not low, dose parathyroid hormone and exogenous Wnt-3a. The increases by strain, PGE2, Wnt-3a, and phorbol 12-myristate 13-acetate were attenuated by inhibition of MEK-1. EGR2 appears to be involved in many of the signaling pathways that constitute early responses of bone cells to strain. These pathways all have multiple functions. Converting their strain-related responses into coherent "instructions" for adaptive (re)modeling is likely to depend upon their contextual activation, suppression, and interaction probably on more than one occasion.
Translated title of the contributionLoading-related regulation of the transcription factor EGR2/Krox-20 in bone cells is
Original languageEnglish
Pages (from-to)3946-3962
Number of pages16
JournalJournal of Biological Chemistry
Volume287
Issue number6
Early online date2 Nov 2011
DOIs
Publication statusPublished - 3 Feb 2012

Keywords

  • Animals
  • Antigens, CD29
  • Bone and Bones
  • Carcinogens
  • Cell Line
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclooxygenase 2
  • Dinoprostone
  • Early Growth Response Protein 2
  • Female
  • Insulin-Like Growth Factor I
  • Integrin beta3
  • MAP Kinase Kinase 1
  • Mice
  • Mitogen-Activated Protein Kinase 3
  • Nitric Oxide
  • RNA, Messenger
  • Receptors, Prostaglandin E, EP1 Subtype
  • Tetradecanoylphorbol Acetate
  • Up-Regulation
  • Wnt Signaling Pathway
  • Wnt3A Protein

Fingerprint Dive into the research topics of 'Loading-related regulation of transcription factor EGR2/Krox-20 in bone cells is ERK1/2 protein-mediated and prostaglandin, Wnt signaling pathway-, and insulin-like growth factor-I axis-dependent'. Together they form a unique fingerprint.

Cite this