阿仑膦酸盐抑制 Sca-1 阳性骨骼干细胞募集，从而削弱甲状旁腺激素对骨重建的合成代谢作用。
Inhibition of Sca-1-positive skeletal stem cell recruitment by alendronate blunts the anabolic effects of parathyroid hormone on bone remodeling.
机构信息
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Cell Stem Cell. 2010 Nov 5;7(5):571-80. doi: 10.1016/j.stem.2010.09.012.
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.
摘要
甲状旁腺激素（PTH）对骨形成的合成作用会被同时使用的抗吸收药物所削弱。我们发现，破骨细胞骨吸收过程中活性转化生长因子（TGF）-β1 的释放会被阿伦膦酸盐抑制。我们表明，小鼠 Sca-1 阳性（Sca-1(+)）骨髓基质细胞是骨骼干细胞亚群，它会在骨吸收时响应活性 TGF-β1 招募到骨重塑部位。阿伦膦酸盐会抑制活性 TGF-β1 的释放以及 Sca-1(+)骨骼干细胞的募集，从而影响骨形成。这一观察结果在 Tgfb1(-/-)小鼠模型中得到了验证，在该模型中，PTH 对骨形成的合成作用减弱。阿伦膦酸盐抑制了 PTH 刺激的注射入小鼠 Sca-1(+)细胞向吸收部位的募集。因此，阿伦膦酸盐抑制活性 TGF-β1 的释放会减少 Sca-1(+)骨骼干细胞的募集，并削弱 PTH 在骨骼中的合成作用。
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本文引用的文献
1
A protocol for isolation and culture of mesenchymal stem cells from mouse compact bone.从鼠密质骨中分离和培养间充质干细胞的方案。
Nat Protoc. 2010 Mar;5(3):550-60. doi: 10.1038/nprot.2009.238. Epub 2010 Feb 25.
2
PTH battles TGF-beta in bone.甲状旁腺激素与 TGF-β在骨骼中相互作用。
Nat Cell Biol. 2010 Mar;12(3):205-7. doi: 10.1038/ncb0310-205.
3
Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis.绝经后骨质疏松症女性中特立帕肽、阿仑膦酸钠或两者联合的疗效。
J Clin Endocrinol Metab. 2010 Apr;95(4):1838-45. doi: 10.1210/jc.2009-1703. Epub 2010 Feb 17.
4
TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling.TGF-β 型 II 受体使 PTH 受体磷酸化以整合骨重塑信号。
Nat Cell Biol. 2010 Mar;12(3):224-34. doi: 10.1038/ncb2022. Epub 2010 Feb 7.
5
TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation.转化生长因子β1诱导的骨间充质干细胞迁移将骨吸收与骨形成联系起来。
Nat Med. 2009 Jul;15(7):757-65. doi: 10.1038/nm.1979. Epub 2009 Jul 5.
6
Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF.低氧诱导因子（HIFs）和血管内皮生长因子（VEGF）对成骨-血管生成偶联的调节作用
J Bone Miner Res. 2009 Aug;24(8):1347-53. doi: 10.1359/jbmr.090602.
7
Endochondral ossification is required for haematopoietic stem-cell niche formation.造血干细胞龛的形成需要软骨内成骨。
Nature. 2009 Jan 22;457(7228):490-4. doi: 10.1038/nature07547. Epub 2008 Dec 10.
8
Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2.多能成体间充质干细胞的高效归巢依赖于FROUNT介导的CCR2聚集。
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9
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