Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin

Alexander Robling, Paul J. Niziolek, Lee A. Baldridge, Keith W. Condon, Matthew Allen, Imranul Alam, Sara M. Mantila, Jelica Gluhak-Heinrich, Teresita Bellido, Stephen E. Harris, Charles H. Turner

Research output: Contribution to journalArticle

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Abstract

Sclerostin, the protein product of the Sost gene, is a potent inhibitor of bone formation. Among bone cells, sclerostin is found nearly exclusively in the osteocytes, the cell type that historically has been implicated in sensing and initiating mechanical signaling. The recent discovery of the antagonistic effects of sclerostin on Lrp5 receptor signaling, a crucial mediator of skeletal mechanotransduction, provides a potential mechanism for the osteocytes to control mechanotransduction, by adjusting their sclerostin (Wnt inhibitory) signal output to modulate Wnt signaling in the effector cell population. We investigated the mechanoregulation of Sost and sclerostin under enhanced (ulnar loading) and reduced (hindlimb unloading) loading conditions. Sost transcripts and sclerostin protein levels were dramatically reduced by ulnar loading. Portions of the ulnar cortex receiving a greater strain stimulus were associated with a greater reduction in Sost staining intensity and sclerostin-positive osteocytes (revealed via in situ hybridization and immunohistochemistry, respectively) than were lower strain portions of the tissue. Hindlimb unloading yielded a significant increase in Sost expression in the tibia. Modulation of sclerostin levels appears to be a finely tuned mechanism by which osteocytes coordinate regional and local osteogenesis in response to increased mechanical stimulation, perhaps via releasing the local inhibition of Wnt/Lrp5 signaling.

Original languageEnglish
Pages (from-to)5866-5875
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number9
DOIs
StatePublished - Feb 29 2008

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Osteocytes
Bone
Hindlimb Suspension
Bone and Bones
Unloading
Osteogenesis
Tibia
In Situ Hybridization
Proteins
Genes
Immunohistochemistry
Cells
Modulation
Tissue
Staining and Labeling
Population

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. / Robling, Alexander; Niziolek, Paul J.; Baldridge, Lee A.; Condon, Keith W.; Allen, Matthew; Alam, Imranul; Mantila, Sara M.; Gluhak-Heinrich, Jelica; Bellido, Teresita; Harris, Stephen E.; Turner, Charles H.

In: Journal of Biological Chemistry, Vol. 283, No. 9, 29.02.2008, p. 5866-5875.

Research output: Contribution to journalArticle

Robling, A, Niziolek, PJ, Baldridge, LA, Condon, KW, Allen, M, Alam, I, Mantila, SM, Gluhak-Heinrich, J, Bellido, T, Harris, SE & Turner, CH 2008, 'Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin', Journal of Biological Chemistry, vol. 283, no. 9, pp. 5866-5875. https://doi.org/10.1074/jbc.M705092200
Robling, Alexander ; Niziolek, Paul J. ; Baldridge, Lee A. ; Condon, Keith W. ; Allen, Matthew ; Alam, Imranul ; Mantila, Sara M. ; Gluhak-Heinrich, Jelica ; Bellido, Teresita ; Harris, Stephen E. ; Turner, Charles H. / Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 9. pp. 5866-5875.
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