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Impacts of GPX4 Haploid Insufficiency on Murine Bone Biomechanical Properties
Author(s) -
Wang Xiaodan,
Gillen Elizabeth Ann,
Meulen Marjolein,
Lei Xin Gen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1068-d
Subject(s) - gpx4 , phospholipid hydroperoxide glutathione peroxidase , endocrinology , medicine , acid phosphatase , chemistry , femoral bone , glutathione peroxidase , selenium , femur , glutathione , andrology , biochemistry , enzyme , surgery , organic chemistry
Selenium‐dependent phospholipid hydroperoxide glutathione peroxidase (GPX4) catalyzes the reduction of phospholipids hydroperoxides and may affect skeletal development by modulating its redox status. Our objective was to determine the impacts of GPX4 hemizygosity on femoral biochemical and mechanical properties of young (2 months of age) and old (12 months of age) female mice. A total of 28 Se‐adequate GPX4 hemizygous (GPX4+/−) mice and their wild‐type (WT) were killed at the two ages to collect femurs for analysis (n = 5 to 9 for each genotype by age). Femoral GPX4 activities in GPX4+/− mice were approximately 30% lower (P < 0.05) than the WT mice at both ages. Femurs of the old GPX4+/− mice had 45% lower (P < 0.05) alkaline phosphatase activity and 1.1‐fold higher (P < 0.05) tartrate resistant acid phosphatase activity than that of WT mice, respectively. However, there was no genotype effect on activities of these two enzymes in the femurs of young mice. The young and old GPX4+/− mice exhibited a 13 and 54% lower (P < 0.05) femoral failure moment than that of the WT mice, respectively, but the difference in the young mice disappeared when the values were normalized by body mass. The old GPX4+/− mice also had higher (P < 0.05) femoral displacement of failure than that of the WT mice. In conclusion, GPx4 haploid insufficiency exerted differential impacts on femoral development and load‐bearing function between the young and the old mice. [NIH DK 53018 to XGL and the College of Engineering LIFE award to EAG]