title: TIEG-null mice display an osteopenic gender-specific phenotype.
abstract: TGFbeta inducible early gene-1 (TIEG) was originally cloned from human osteoblasts (OB) and has been shown to play an important role in TGFbeta/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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Hawse
authors.forename: U T
authors.initials: UT
authors.lastname: Iwaniec
authors.forename: S F
authors.initials: SF
authors.lastname: Bensamoun
authors.forename: D G
authors.initials: DG
authors.lastname: Monroe
authors.forename: K D
authors.initials: KD
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Ilharreborde
authors.forename: N M
authors.initials: NM
authors.lastname: Rajamannan
authors.forename: M J
authors.initials: MJ
authors.lastname: Oursler
authors.forename: R T
authors.initials: RT
authors.lastname: Turner
authors.forename: T C
authors.initials: TC
authors.lastname: Spelsberg
authors.forename: M
authors.initials: M
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000166:cytology / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D013977:Tibia / Q000166:cytology / Q000473:pathology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors