Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell Stem Cell. 2010 Nov 5;7(5):571-80. doi: 10.1016/j.stem.2010.09.012.
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.
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。
