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p47phox-Nox2-dependent ROS Signaling Inhibits Early Bone Development in Mice but Protects against Skeletal Aging

Jin-Ran Chen1, Oxana P Lazarenko2, Michael L Blackburn2

  • 1From the Arkansas Children's Nutrition Center and the Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202 chenjinran@uams.edu.

The Journal of Biological Chemistry
|April 30, 2015
PubMed

Insights

Reduced reactive oxygen species (ROS) signaling in p47(phox-/-) mice leads to age-related bone loss. This occurs through increased inflammation and senescence, indicating ROS signaling suppresses aging-related bone inflammation.

Area of Science:

  • Bone Biology
  • Aging Research
  • Inflammation

Background:

  • Bone remodeling is tightly regulated by age, with aging often associated with increased reactive oxygen species (ROS).
  • The role of reduced ROS signaling in bone inflammation and remodeling during aging remains largely unexplored.
  • The p47(phox) protein is a crucial component of the Nox2 oxidase complex, essential for ROS production.

Purpose of the Study:

  • To investigate the impact of impaired Nox2 function (loss of p47(phox)) on bone metabolism and aging.
  • To elucidate the mechanisms by which reduced ROS signaling affects bone remodeling, inflammation, and senescence.
  • To determine if physiological ROS signaling plays a protective role against age-related bone changes.

Main Methods:

  • Utilized p47(phox) knock-out (p47(phox-/-)) mice and age-matched wild-type controls.
  • Assessed bone mass and strength at 6 weeks and 2 years of age.
  • Analyzed ROS generation, p47(phox)-Nox2 signaling, senescence-associated secretory phenotype, and inflammation in vivo and in ex vivo cell cultures.

Main Results:

  • p47(phox-/-) mice exhibited an age-related switch in bone mass and strength compared to controls.
  • Younger p47(phox-/-) mice showed increased bone formation, while older mice displayed decreased bone mass.
  • Older p47(phox-/-) mice had increased senescence and inflammation in bone, despite reduced ROS generation.

Conclusions:

  • The age-related decline in bone mass in p47(phox)-deficient mice is driven by an exacerbated inflammatory environment.
  • Physiological ROS signaling mediated by p47(phox)-Nox2 is critical for suppressing inflammation during aging.
  • Impaired ROS production contributes to accelerated bone senescence and inflammation, highlighting a protective role of ROS in bone aging.
Keywords:
TNFαagingosteoblastreactive oxygen species

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