Unraveling the role of FoxOs in bone--insights from mouse models

Bone. 2011 Sep;49(3):319-27. doi: 10.1016/j.bone.2011.05.023. Epub 2011 Jun 1.

Abstract

The FoxO subfamily of forkhead transcription factors plays a critical role in a variety of physiological processes including metabolism, differentiation, proliferation, apoptosis and protection from stress. FoxO activity is inhibited by growth factors and the insulin signaling pathways and stimulated by nutrient depletion and a plethora of reactive oxygen species (ROS)-induced post-translational modifications. Recent studies have uncovered a fundamental role for FoxOs in skeletal homeostasis. In cells of the osteoblast lineage, FoxOs modulate redox balance, protein synthesis, and differentiation through the activation of specific gene programs and interaction with other transcription factors and co-factors such as β-catenin, ATF-4, and Runx2. FoxO activation also attenuates osteoclastogenesis through both cell autonomous and indirect mechanisms. In this review I discuss recent advances in the understanding of FoxO specific actions in osteoblast progenitors, osteoblasts, and osteoclast, as well as the implications of FoxO activation for age-related skeletal involution.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bone and Bones / cytology
  • Bone and Bones / physiology*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Homeostasis
  • Insulin / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Models, Animal*
  • Osteoblasts / cytology
  • Osteoblasts / physiology*
  • Osteoclasts / cytology
  • Osteoclasts / physiology
  • Oxidation-Reduction
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Protein Processing, Post-Translational
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology

Substances

  • Forkhead Transcription Factors
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Protein Isoforms
  • Reactive Oxygen Species