Skeletal tissue regulation by catalase overexpression in mitochondria
| Autor: | Akhhilesh Kumar, Joshua S. Alwood, Eric L. Moyer, Samantha Torres, Ruth K. Globus, Candice Tahimic, Ann-Sofie Schreurs, Tiffany Truong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging Physiology Mice Transgenic 030209 endocrinology & metabolism Mitochondrion medicine.disease_cause Bone and Bones Skeletal tissue Oxidative damage Mice 03 medical and health sciences 0302 clinical medicine Osteoclast medicine Animals Humans chemistry.chemical_classification Reactive oxygen species biology Osteoblast Hydrogen Peroxide Cell Biology Catalase Mitochondria Cell biology Oxidative Stress 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation chemistry biology.protein Lipid Peroxidation Reactive Oxygen Species Oxidation-Reduction Oxidative stress |
| Zdroj: | American Journal of Physiology-Cell Physiology. 319:C734-C745 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00068.2020 |
| Popis: | Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wild-type (WT) mice and transgenic mice (male, 16 wk of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hind-limb unloading and exposure to ionizing radiation (137Cs, 2 Gy). Treatment for 2 wk caused lipid peroxidation in the bones WT but not mCAT mice, showing that transgene expression mitigated oxidative stress. Ex vivo osteoblast colony growth rate was 95% greater in mCAT than WT mice and correlated with catalase activity levels ( P < 0.005, r = 0.67), although terminal osteoblast and osteoclast differentiation were unaffected. mCAT mice had lower cancellous bone volume and cortical size than WT mice. Ambulatory control mCAT animals also displayed reduced cancellous and cortical structural properties compared with control WT mice. In mCAT but not WT mice, treatment caused an unexpectedly rapid radial expansion (+8% cortical area, +22% moment of inertia), reminiscent of compensatory bone growth during advancing age. In contrast, treatment caused similar structural deficits in cancellous tissue of mCAT and WT mice. In sum, mitochondrial ROS signaling via H2O2 was important for the acquisition of adult bone structure and catalase overexpression failed to protect cancellous tissue from treatment. In contrast, catabolic stimuli caused radial expansion in mCAT not WT mice, suggesting that mitochondrial ROS in skeletal cells act to suppress tissue turnover in response to remodeling challenges. |
| Databáze: | OpenAIRE |
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