The effects of GATA-1 and NF-E2 deficiency on bone biomechanical, biochemical, and mineral properties.
Mice deficient in GATA-1 or NF-E2, transcription factors required for normal megakaryocyte (MK) development, have increased numbers of MKs, reduced numbers of platelets, and a striking high bone mass phenotype. Here, we show the bone geometry, microarchitecture, biomechanical, biochemical, and mineral properties from these mutant mice. We found that the outer geometry of the mutant bones was similar to controls, but that both mutants had a striking increase in total bone area (up to a 35% increase) and trabecular bone area (up to a 19% increase). Interestingly, only the NF-E2 deficient mice had a significant increase in cortical bone area (21%) and cortical thickness (27%), which is consistent with the increase in bone mineral density (BMD) seen only in the NF-E2 deficient femurs. Both mutant femurs exhibited significant increases in several biomechanical properties including peak load (up to a 32% increase) and stiffness (up to a 13% increase). Importantly, the data also demonstrate differences between the two mutant mice. GATA-1 deficient femurs break in a ductile manner, whereas NF-E2 deficient femurs are brittle in nature. To better understand these differences, we examined the mineral properties of these bones. Although none of the parameters measured were different between the NF-E2 deficient and control mice, an increase in calcium (21%) and an increase in the mineral/matrix ratio (32%) was observed in GATA-1 deficient mice. These findings appear to contradict biomechanical findings, suggesting the need for further research into the mechanisms by which GATA-1 and NF-E2 deficiency alter the material properties of bone.
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. mkacena@iupui.edu
Melissa A
MA
Kacena
Caren M
CM
Gundberg
William J
WJ
Kacena
William J
WJ
Landis
Adele L
AL
Boskey
Mary L
ML
Bouxsein
Mark C
MC
Horowitz
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000502:physiology; D050982:GATA1 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism
D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D002118:Calcium