The role of osteoclast differentiation and function in skeletal homeostasis

J Biochem. 2016 Jan;159(1):1-8. doi: 10.1093/jb/mvv112. Epub 2015 Nov 3.

Abstract

Osteoclasts are giant multinucleated cells that differentiate from hematopoietic cells in the bone marrow and carry out important physiological functions in the regulation of skeletal homeostasis as well as hematopoiesis. Osteoclast biology shares many features and components with cells of the immune system, including cytokine-receptor interactions (RANKL-RANK), intracellular signalling molecules (TRAF6) and transcription factors (NFATc1). Although the roles of these molecules in osteoclast differentiation are well known, fundamental questions remain unsolved, including the exact location of the RANKL-RANK interaction and the in vivo temporal and spatial information on the transformation of hematopoietic cells into bone-resorbing osteoclasts. This review focuses on the importance of cell-cell contact and metabolic adaptation for differentiation, relatively overlooked aspects of osteoclast biology and biochemistry.

Keywords: PGC-1β; glutaminolysis; glycolysis; iron; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Development / physiology*
  • Bone Marrow Cells / physiology
  • Bone and Bones / physiology*
  • Cell Differentiation / physiology*
  • Cell Proliferation / physiology
  • Homeostasis / physiology
  • Humans
  • Mice
  • NFATC Transcription Factors / metabolism
  • Osteoblasts / physiology
  • Osteoclasts / cytology*
  • RANK Ligand / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Signal Transduction
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • NFATC Transcription Factors
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNF Receptor-Associated Factor 6