TIEG-null mice display an osteopenic gender-specific phenotype

J. R. Hawse, U. T. Iwaniec, S. F. Bensamoun, D. G. Monroe, K. D. Peters, B. Ilharreborde, N. M. Rajamannan, M. J. Oursler, R. T. Turner, T. C. Spelsberg, M. Subramaniam

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

TGFβ inducible early gene-1 (TIEG) was originally cloned from human osteoblasts (OB) and has been shown to play an important role in TGFβ/Smad signaling, regulation of gene expression and OB growth and differentiation. To better understand the biological role of TIEG in the skeleton, we have generated congenic TIEG-null (TIEG-/-) mice in a pure C57BL/6 background. Through the use of DXA and pQCT analysis, we have demonstrated that the femurs and tibias of two-month-old female TIEG-/- mice display significant decreases in total bone mineral content, density, and area relative to wild-type (WT) littermates. However, no differences were observed for any of these bone parameters in male mice. Further characterization of the bone phenotype of female TIEG-/- mice involved mechanical 3-point bending tests, micro-CT, and histomorphometric analyses of bone. The 3-point bending tests revealed that the femurs of female TIEG-/- mice have reduced strength with increased flexibility compared to WT littermates. Micro-CT analysis of femurs of two-month-old female TIEG-/- mice revealed significant decreases in cortical bone parameters compared to WT littermates. Histomorphometric evaluation of the distal femur revealed that female TIEG-/- mice also display a 31% decrease in cancellous bone area, which is primarily due to a decrease in trabecular number. At the cellular level, female TIEG-/- mice exhibit a 42% reduction in bone formation rate which is almost entirely due to a reduction in double labeled perimeter. Differences in mineral apposition rate were not detected between WT and TIEG-/- mice. Taken together, these findings suggest that female TIEG-/- mice are osteopenic mainly due to a decrease in the total number of functional/mature OBs.

Original languageEnglish (US)
Pages (from-to)1025-1031
Number of pages7
JournalBone
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Bone
  • Knockout mice
  • Osteoblast
  • Osteopenia
  • TIEG

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Hawse, J. R., Iwaniec, U. T., Bensamoun, S. F., Monroe, D. G., Peters, K. D., Ilharreborde, B., Rajamannan, N. M., Oursler, M. J., Turner, R. T., Spelsberg, T. C., & Subramaniam, M. (2008). TIEG-null mice display an osteopenic gender-specific phenotype. Bone, 42(6), 1025-1031. https://doi.org/10.1016/j.bone.2008.02.004