Control of bone resorption in mice by Schnurri-3

Proc Natl Acad Sci U S A. 2012 May 22;109(21):8173-8. doi: 10.1073/pnas.1205848109. Epub 2012 May 9.


Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Bone Resorption / genetics
  • Bone Resorption / physiopathology*
  • Cells, Cultured
  • Coculture Techniques
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Hyperparathyroidism, Secondary / genetics
  • Hyperparathyroidism, Secondary / physiopathology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts / cytology
  • Osteoblasts / physiology*
  • Osteoclasts / cytology
  • Osteoclasts / physiology*
  • Phenotype
  • RANK Ligand / metabolism
  • Regulatory Elements, Transcriptional / physiology
  • Skull / cytology


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • RANK Ligand
  • Schnurri-3 protein, mouse