title: TGFβ inducible early gene-1 plays an important role in mediating estrogen signaling in the skeleton.
abstract: TGFβ Inducible Early Gene-1 (TIEG1) knockout (KO) mice display a sex-specific osteopenic phenotype characterized by low bone mineral density, bone mineral content, and overall loss of bone strength in female mice. We, therefore, speculated that loss of TIEG1 expression would impair the actions of estrogen on bone in female mice. To test this hypothesis, we employed an ovariectomy (OVX) and estrogen replacement model system to comprehensively analyze the role of TIEG1 in mediating estrogen signaling in bone at the tissue, cell, and biochemical level. Dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-CT analyses revealed that loss of TIEG1 expression diminished the effects of estrogen throughout the skeleton and within multiple bone compartments. Estrogen exposure also led to reductions in bone formation rates and mineralizing perimeter in wild-type mice with little to no effects on these parameters in TIEG1 KO mice. Osteoclast perimeter per bone perimeter and resorptive activity as determined by serum levels of CTX-1 were differentially regulated after estrogen treatment in TIEG1 KO mice compared with wild-type littermates. No significant differences were detected in serum levels of P1NP between wild-type and TIEG1 KO mice. Taken together, these data implicate an important role for TIEG1 in mediating estrogen signaling throughout the mouse skeleton and suggest that defects in this pathway are likely to contribute to the sex-specific osteopenic phenotype observed in female TIEG1 KO mice.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Hawse
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Pitel
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Cicek
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Philbrick
authors.forename: Anne
authors.initials: A
authors.lastname: Gingery
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Peters
authors.forename: Farhan A
authors.initials: FA
authors.lastname: Syed
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Urszula T
authors.initials: UT
authors.lastname: Iwaniec
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Spelsberg
authors.forename: Malayannan
authors.initials: M
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D004967:Estrogens; D014157:Transcription Factors; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
keywords: BONE; ESTROGEN; KRÜPPEL-LIKE TRANSCRIPTION FACTOR 10 (KLF10); OSTEOBLAST; OSTEOCLAST; OVARIECTOMY; TGFβ INDUCIBLE EARLY GENE-1 (TIEG1)