Inhibition of sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling

Xiangwei Wu, Lijuan Pang, Weiqi Lei, William Lu, Jun Li, Zhaoyang Li, Frank J. Frassica, Xueling Chen, Mei Wan, Xu Cao

Research output: Contribution to journalArticle

Abstract

The anabolic effects of parathyroid hormone (PTH) on bone formation are impaired by concurrent use of antiresorptive drugs. We found that the release of active transforming growth factor (TGF)-β1 during osteoclastic bone resorption is inhibited by alendronate. We showed that mouse Sca-1-positive (Sca-1+) bone marrow stromal cells are a skeletal stem cell subset, which are recruited to bone remodeling sites by active TGF-β1 in response to bone resorption. Alendronate inhibits the release of active TGF-β1 and the recruitment of Sca-1+ skeletal stem cells for the bone formation. The observation was validated in a Tgfb1-/- mouse model, in which the anabolic effects of PTH on bone formation are diminished. The PTH-stimulated recruitment of injected mouse Sca-1+ cells to the resorptive sites was inhibited by alendronate. Thus, inhibition of active TGF-β1 release by alendronate reduces the recruitment of Sca-1+ skeletal stem cells and impairs the anabolic action of PTH in bone.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalCell Stem Cell
Volume7
Issue number5
DOIs
StatePublished - Nov 5 2010

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Anabolic Agents
Alendronate
Bone Remodeling
Transforming Growth Factors
Parathyroid Hormone
Stem Cells
Osteogenesis
Bone Resorption
Bone Density Conservation Agents
Mesenchymal Stromal Cells
Catalytic Domain
Observation
Bone and Bones

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Inhibition of sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling. / Wu, Xiangwei; Pang, Lijuan; Lei, Weiqi; Lu, William; Li, Jun; Li, Zhaoyang; Frassica, Frank J.; Chen, Xueling; Wan, Mei; Cao, Xu.

In: Cell Stem Cell, Vol. 7, No. 5, 05.11.2010, p. 571-580.

Research output: Contribution to journalArticle

Wu, Xiangwei ; Pang, Lijuan ; Lei, Weiqi ; Lu, William ; Li, Jun ; Li, Zhaoyang ; Frassica, Frank J. ; Chen, Xueling ; Wan, Mei ; Cao, Xu. / Inhibition of sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling. In: Cell Stem Cell. 2010 ; Vol. 7, No. 5. pp. 571-580.
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