Knockout of SOD1 or GPX1 led to decreased bone remodeling in young adult female mice
2007; Wiley; Volume: 21; Issue: 5 Linguagem: Inglês
10.1096/fasebj.21.5.a114-d
ISSN1530-6860
Autores Tópico(s)Bone Metabolism and Diseases
ResumoAlthough reactive oxygen species are constantly generated from bone metabolism, the in vivo role of antioxidant enzymes in bone remodeling remains unclear. The objective of this study was to determine impacts of knockout of Cu, Zn-superoxide dismutase (SOD1) or Se-dependent glutathione peroxidase-1 (GPX1) and double knockout (DKO) of SOD1 and GPX1 on morphology and gene expression associated with bone remodeling. Femurs were isolated from SOD1−/−, GPX1−/−, DKO, and their wild-type (WT) female mice (8-week old) to assay for bone formation, resorption, and mineralization. While SOD1−/− and GPX1−/−mice showed a 54 to 74% decrease (P <0.01) of osteoblasts and osteoclasts than those of WT, while DKO had no such changes. However, the three knockout groups displayed similar reductions in mineralization (43 to 52%; P < 0.001) and total carbonic anhydrase activity in osteoclasts (82 to 85%; P < 0.0001), compared with the WT. Semi quantitative RT-PCR showed up-regulation of signal transducer and activator of transcription 1 (STAT1) gene in all three knockout groups and down-regulation of basic helix-loop-helix domain containing class B2 (BHLHB2) and carbonic anhydrase II genes only in single knockout groups. Bone sialoprotein (SPP1) gene was down regulated in SOD1−/− mice, but up-regulated in DKO mice. In conclusion, knockout of SOD1 or GPX1 suppressed femur bone remodeling, but double knockout of both enzymes exerted different impacts. (NIH DK 53018 TO XGL)
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