FoxO-Mediated Defense against Oxidative Stress in Osteoblasts Is Indispensable for Skeletal Homeostasis in Mice Academic Article uri icon


MeSH Major

  • Forkhead Transcription Factors
  • Osteoblasts
  • Oxidative Stress


  • Aging increases oxidative stress and osteoblast apoptosis and decreases bone mass, whereas forkhead box O (FoxO) transcription factors defend against oxidative stress by activating genes involved in free radical scavenging and apoptosis. Conditional deletion of FoxO1, FoxO3, and FoxO4 in 3-month-old mice resulted in an increase in oxidative stress in bone and osteoblast apoptosis and a decrease in the number of osteoblasts, the rate of bone formation, and bone mass at cancellous and cortical sites. The effect of the deletion on osteoblast apoptosis was cell autonomous and resulted from oxidative stress. Conversely, overexpression of a FoxO3 transgene in mature osteoblasts decreased oxidative stress and osteoblast apoptosis and increased osteoblast number, bone formation rate, and vertebral bone mass. We conclude that FoxO-dependent oxidative defense provides a mechanism to handle the oxygen free radicals constantly generated by the aerobic metabolism of osteoblasts and is thereby indispensable for bone mass homeostasis.

publication date

  • February 3, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2819984

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2009.12.009

PubMed ID

  • 20142101

Additional Document Info

start page

  • 136

end page

  • 46


  • 11


  • 2