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Inhibition of Sca-1-Positive Skeletal Stem Cell Recruitment by Alendronate Blunts the Anabolic Effects of Parathyroid Hormone on Bone Remodeling

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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 [4]Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong 999777, Hong Kong, Peoples R China
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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.

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出版当年[2009]版:
大类 | 1 区 生物
小类 | 1 区 细胞生物学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 细胞与组织工程 1 区 细胞生物学
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出版当年[2008]版:
Q1 CELL BIOLOGY
最新[2023]版:
Q1 CELL & TISSUE ENGINEERING Q1 CELL BIOLOGY

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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
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