FoxO-mediated Defense Against Oxidative Stress in Osteoblasts is Indispensable for Skeletal Homeostasis in Mice

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2010 Feb 10

PMID 20142101

Citations 175

Authors

Elena Ambrogini

Maria Almeida

Marta Martin-Millan

Ji-Hye Paik

Ronald A DePinho

Li Han

Joseph Goellner

Robert S Weinstein

Robert L Jilka

Charles A OBrien

Stavros C Manolagas

Affiliations

Soon will be listed here.

Abstract

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.

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