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Title: Skeletal tissue regulation by catalase overexpression in mitochondria

Journal Article · · American Journal of Physiology: Cell Physiology
 [1];  [2];  [2];  [2];  [1];  [3];  [4];  [4]
  1. Space Biosciences Division, NASA Ames Research Center, Moffett Field, California; Universities Space Research Association, Moffett Field, California
  2. Space Biosciences Division, NASA Ames Research Center, Moffett Field, California; Blue Marble Space Institute of Science, Seattle, Washington
  3. Space Biosciences Division, NASA Ames Research Center, Moffett Field, California; KBR, Moffett Field, California
  4. Space Biosciences Division, NASA Ames Research Center, Moffett Field, California
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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 H2O2was 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.

Research Organization:
NASA Ames Research Center (ARC), Moffett Field, Mountain View, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
DOE Contract Number:
SC0001507
OSTI ID:
1850744
Journal Information:
American Journal of Physiology: Cell Physiology, Vol. 319, Issue 4; ISSN 0363-6143
Publisher:
American Physiological Society
Country of Publication:
United States
Language:
English

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