TGFbeta inducible early gene-1 knockout mice display defects in bone strength and microarchitecture.
TGFbeta inducible early gene-1 (TIEG) is a member of the Sp/Krüppel-like transcription factor family originally cloned from human osteoblasts. We have previously demonstrated that TIEG plays a role in the expression of important osteoblast marker genes and in the maturation/differentiation of osteoblasts. To elucidate the function of TIEG in skeletal development and maintenance, we have generated a TIEG knockout (KO) mouse. Three-point bending tests demonstrated that the femurs of TIEG KO mice are significantly weaker than those of wild-type animals. pQCT analysis of tibias revealed significant decreases in bone content, density and size in KO animals compared to wild-type mice. Micro-CT analysis of the femoral head and vertebrae revealed increases in femoral head trabecular separation and decreases in cortical bone thickness and vertebral bone volume in KO mice relative to wild-type controls. In addition, electron microscopy indicated a significant decrease in osteocyte number in the femurs of KO mice. Taken together, these data demonstrate that the bones of TIEG KO mice display an osteopenic phenotype with significantly weaker bones and reduced amounts of cortical and trabecular bone. In summary, an important role for TIEG in skeletal development and/or homeostasis is indicated.
Bensamoun
Sabine F
SF
Department of Orthopedic Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hawse
John R
JR
Subramaniam
Malayannan
M
Ilharreborde
Brice
B
Bassillais
Armelle
A
Benhamou
Claude L
CL
Fraser
Daniel G
DG
Oursler
Merry J
MJ
Amadio
Peter C
PC
An
Kai-Nan
KN
Spelsberg
Thomas C
TC
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology* / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D010011:Osteocytes / Q000473:pathology; D013131:Spine / Q000473:pathology / Q000503:physiopathology; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C569958:KLF10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D051765:Early Growth Response Transcription Factors