title: Early growth response gene 1 regulates bone properties in mice.
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.
authors.affiliation: Bone Cell Biology and Imaging Laboratory, Caspary Research Building, Rm. 623, Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Reumann
authors.forename: Olga
authors.initials: O
authors.lastname: Strachna
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Lukashova
authors.forename: Kostas
authors.initials: K
authors.lastname: Verdelis
authors.forename: Eve
authors.initials: E
authors.lastname: Donnelly
authors.forename: Adele L
authors.initials: AL
authors.lastname: Boskey
authors.forename: Philipp
authors.initials: P
authors.lastname: Mayer-Kuckuk
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging*; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014057:Tomography, X-Ray Computed
chemical_list: D051766:Early Growth Response Protein 1