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)-beta 1 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-beta 1 in response to bone resorption. Alendronate inhibits the release of active TGF-beta 1 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-beta 1 release by alendronate reduces the recruitment of Sca-1(+) skeletal stem cells and impairs the anabolic action of PTH in bone.
基金:
US National Institutes of Health [DK0080898, AR 053973]
第一作者单位:[1]Johns Hopkins Univ, Sch Med, Dept Orthopaed Surg, Baltimore, MD 21205 USA[2]Huazhong Univ Sci & Technol, Tongji Med Sch, Tongji Hosp, Wuhan 430030, Hubei, Peoples R China[3]Shihezi Univ, Sch Med, Shihezi 832002, Xinjiang, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Wu Xiangwei,Pang Lijuan,Lei Weiqi,et al.Inhibition of Sca-1-Positive Skeletal Stem Cell Recruitment by Alendronate Blunts the Anabolic Effects of Parathyroid Hormone on Bone Remodeling[J].CELL STEM CELL.2010,7(5):571-580.doi:10.1016/j.stem.2010.09.012.
APA:
Wu, Xiangwei,Pang, Lijuan,Lei, Weiqi,Lu, William,Li, Jun...&Cao, Xu.(2010).Inhibition of Sca-1-Positive Skeletal Stem Cell Recruitment by Alendronate Blunts the Anabolic Effects of Parathyroid Hormone on Bone Remodeling.CELL STEM CELL,7,(5)
MLA:
Wu, Xiangwei,et al."Inhibition of Sca-1-Positive Skeletal Stem Cell Recruitment by Alendronate Blunts the Anabolic Effects of Parathyroid Hormone on Bone Remodeling".CELL STEM CELL 7..5(2010):571-580