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Early Growth Response Gene 1 Regulates Bone Properties in Mice

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Abstract

Transcriptional regulation of the postnatal skeleton is incompletely understood. Here, we determined the consequence of loss of early growth response gene 1 (EGR-1) on bone properties. Analyses were performed on both the microscopic and molecular levels utilizing micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FTIRI), respectively. Mice deficient in EGR-1 (Egr-1 −/−) were studied and compared to sex- and age-matched wild-type (wt) control animals. Femoral trabecular bone in male Egr-1 −/− mice demonstrated osteopenic characteristics marked by reductions in both bone volume fraction (BV/TV) and bone mineral density (BMD). Morphological analysis revealed fewer trabeculae in these animals. In contrast, female Egr-1 −/− animals had thinner trabeculae, but BV/TV and BMD were not significantly reduced. Analysis of femoral cortical bone at the mid-diaphysis did not show significant osteopenic characteristics but detected changes in cross-sectional geometry in both male and female Egr-1 −/− animals. Functionally, this resulted in decreased resistance to three-point bending as indicated by a reduction in maximum load, failure load, and stiffness. Assessment of compositional bone properties, including mineral-to-matrix ratio, carbonate-to-phosphate ratio, crystallinity, and cross-linking, in femurs by FTIRI did not show any significant differences or an appreciable trend between Egr-1 −/− and wt mice of either sex. Unexpectedly, rib bone from Egr-1 −/− animals displayed distinct osteopenic traits that were particularly pronounced in female mice. This study provides genetic evidence that both sex and skeletal site are critical determinants of EGR-1 activity in vivo and that its site-specific action may contribute to the mechanical properties of bone.

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Acknowledgements

We thank Kirsten Stoner for skilled execution and interpretation of mechanical bone testing, Ashley Acosta for expert data collection and analysis, and Dr. Marjolein van der Meulen for critical comments on the manuscript. This work was supported by NIH grants R01AR055294 (P. M.-K.) and P30AR046121 (A. L. B.) as well as the postdoctoral fellowship F32AR056148 (E. D.).

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Authors and Affiliations

  1. Bone Cell Biology and Imaging Laboratory, Caspary Research Building, Rm. 623, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA

    Marie K. Reumann, Olga Strachna & Philipp Mayer-Kuckuk

  2. Mineralized Tissue Laboratory, Hospital for Special Surgery, New York, USA

    Lyudmila Lukashova, Kostas Verdelis, Eve Donnelly & Adele L. Boskey

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  1. Marie K. Reumann
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  2. Olga Strachna
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Correspondence to Philipp Mayer-Kuckuk.

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Reumann, M.K., Strachna, O., Lukashova, L. et al. Early Growth Response Gene 1 Regulates Bone Properties in Mice. Calcif Tissue Int 89, 1–9 (2011). https://doi.org/10.1007/s00223-011-9486-0

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