Evidence for osteocyte regulation of bone homeostasis through RANKL expression

Nat Med. 2011 Sep 11;17(10):1231-4. doi: 10.1038/nm.2452.


Osteocytes embedded in bone have been postulated to orchestrate bone homeostasis by regulating both bone-forming osteoblasts and bone-resorbing osteoclasts. We find here that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells. Furthermore, the severe osteopetrotic phenotype that we observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / physiology*
  • Cell Differentiation / physiology
  • Femur / cytology
  • Femur / diagnostic imaging
  • Flow Cytometry
  • Gene Expression Profiling
  • Green Fluorescent Proteins / metabolism
  • Homeostasis / physiology*
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Osteoclasts / metabolism
  • Osteoclasts / physiology
  • Osteocytes / metabolism*
  • Osteocytes / physiology
  • Osteopetrosis / metabolism*
  • RANK Ligand / deficiency
  • RANK Ligand / metabolism*
  • Real-Time Polymerase Chain Reaction
  • X-Ray Microtomography


  • RANK Ligand
  • Tnfsf11 protein, mouse
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins