Bone phenotype of the aromatase deficient mouse

Orhan K. Öz, Gen Hirasawa, Jonathan Lawson, Lydia Nanu, Anca Constantinescu, Peter P. Antich, Ralph P. Mason, Edward Tsyganov, Robert W. Parkey, Joseph E. Zerwekh, Evan R. Simpson

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (μCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.

Original languageEnglish (US)
Pages (from-to)49-59
Number of pages11
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume79
Issue number1-5
DOIs
Publication statusPublished - 2001

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Keywords

  • Aromatase
  • Bone
  • Dual energy X-ray absorptiometry
  • Estrogen
  • Histomorphometry
  • Insulin-like growth factor 1
  • Major urinary protein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Öz, O. K., Hirasawa, G., Lawson, J., Nanu, L., Constantinescu, A., Antich, P. P., ... Simpson, E. R. (2001). Bone phenotype of the aromatase deficient mouse. Journal of Steroid Biochemistry and Molecular Biology, 79(1-5), 49-59. https://doi.org/10.1016/S0960-0760(01)00130-3