TGFβ inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton

John R. Hawse, Kevin S. Pitel, Muzaffer Cicek, Kenneth A. Philbrick, Anne Gingery, Kenneth D. Peters, Farhan A. Syed, James N. Ingle, Vera J. Suman, Urszula T. Iwaniec, Russell T. Turner, Thomas C. Spelsberg, Malayannan Subramaniam

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

TGFβ Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a sex-specific osteopenic phenotype characterized by low bone mineral density, bone mineral content, and overall loss of bone strength in female mice. We, therefore, speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. To test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell, and biochemical level. Dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter and resorptive activity as determined by serum levels of CTX-1 were differentially regulated after estrogen treatment in TIEG1 KO mice compared with wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the sex-specific osteopenic phenotype observed in female TIEG1 KO mice.

Original languageEnglish (US)
Pages (from-to)1206-1216
Number of pages11
JournalJournal of Bone and Mineral Research
Volume29
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • Krüppel-like transcription factor 10 (KLF10)
  • TGFβ inducible early gene-1 (TIEG1)
  • bone
  • estrogen
  • osteoblast
  • osteoclast
  • ovariectomy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Hawse, J. R., Pitel, K. S., Cicek, M., Philbrick, K. A., Gingery, A., Peters, K. D., Syed, F. A., Ingle, J. N., Suman, V. J., Iwaniec, U. T., Turner, R. T., Spelsberg, T. C., & Subramaniam, M. (2014). TGFβ inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton. Journal of Bone and Mineral Research, 29(5), 1206-1216. https://doi.org/10.1002/jbmr.2142