Osthole stimulates osteoblast differentiation and bone formation by activation of beta-catenin-BMP signaling.
Osthole stimulates osteoblast differentiation and bone formation by activation of beta-catenin-BMP signaling.
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oSthole通过激活β-catenin-BMP信号传导刺激成骨细胞分化和骨形成。
DOI：
10.1002/jbmr.21
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发表时间：
2010-06
影响因子：
6.2
通讯作者：
Wang, Yong-Jun
中科院分区：
文献类型：
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作者：
Tang, De-Zhi;Hou, Wei;Zhou, Quan;Zhang, Minjie;Holz, Jonathan;Sheu, Tzong-Jen;Li, Tian-Fang;Cheng, Shao-Dan;Shi, Qi;Harris, Stephen E.;Chen, Di;Wang, Yong-Jun
骨质疏松症的定义是骨密度降低，并有很高的脆性骨折风险。目前可用的治疗方案包括抗吸收药物，如雌激素受体类似物和二磷酸，以及合成代谢药物，如甲状旁腺激素(PTH)。然而，由于不利影响，这两种选择都不是完全令人满意的。因此，寻找新的合成代谢药物以改善未来的骨质疏松症治疗是非常必要的。蛇床子素是一种从中药中提取的香豆素类衍生物，已被证明具有刺激成骨细胞增殖和分化的作用，但其在体内对骨形成的影响及其机制尚不清楚。在本研究中，我们发现局部注射蛇床子素显著增加了小鼠颅骨表面的新骨形成。卵巢切除导致大鼠明显的骨丢失，而蛇床子素在很大程度上阻止了这种丢失，改善了骨微结构、组织形态计量学参数和生物力学特性。体外研究表明，蛇床子素可激活Wnt/β-catenin信号转导通路，增加骨形态发生蛋白2的表达，促进成骨细胞分化。β-连环蛋白和骨形态发生蛋白2基因的靶向缺失消除了蛇床子素对成骨细胞分化的刺激作用。由于BMP2基因的缺失不影响蛇床子素诱导的β-连环蛋白的表达，而β-连环蛋白基因的缺失抑制了蛇床子素调控的成骨细胞BMP2的表达，因此我们认为蛇床子素通过β-连环蛋白-骨形态发生蛋白信号途径促进成骨细胞的分化。我们的研究结果表明，蛇床子素可能是一种潜在的合成代谢药物，可以刺激骨形成，防止雌激素缺乏所致的骨丢失。©2010美国骨与矿物研究学会。
Osteoporosis is defined as reduced bone mineral density with a high risk of fragile fracture. Current available treatment regimens include antiresorptive drugs such as estrogen receptor analogues and bisphosphates and anabolic agents such as parathyroid hormone (PTH). However, neither option is completely satisfactory because of adverse effects. It is thus highly desirable to identify novel anabolic agents to improve future osteoporosis treatment. Osthole, a coumarin-like derivative extracted from Chinese herbs, has been shown to stimulate osteoblast proliferation and differentiation, but its effect on bone formation in vivo and underlying mechanism remain unknown. In this study, we found that local injection of Osthole significantly increased new bone formation on the surface of mouse calvaria. Ovariectomy caused evident bone loss in rats, whereas Osthole largely prevented such loss, as shown by improved bone microarchitecture, histomorphometric parameters, and biomechanical properties. In vitro studies demonstrated that Osthole activated Wnt/β-catenin signaling, increased Bmp2 expression, and stimulated osteoblast differentiation. Targeted deletion of the β-catenin and Bmp2 genes abolished the stimulatory effect of Osthole on osteoblast differentiation. Since deletion of the Bmp2 gene did not affect Osthole-induced β-catenin expression and the deletion of the β-catenin gene inhibited Osthole-regulated Bmp2 expression in osteoblasts, we propose that Osthole acts through β-catenin–BMP signaling to promote osteoblast differentiation. Our findings demonstrate that Osthole could be a potential anabolic agent to stimulate bone formation and prevent estrogen deficiency–induced bone loss. © 2010 American Society for Bone and Mineral Research.
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影响因子：
9.8
作者：
Styrkarsdottir U;Cazier JB;Kong A;Rolfsson O;Larsen H;Bjarnadottir E;Johannsdottir VD;Sigurdardottir MS;Bagger Y;Christiansen C;Reynisdottir I;Grant SF;Jonasson K;Frigge ML;Gulcher JR;Sigurdsson G;Stefansson K
通讯作者：
Stefansson K
影响因子：
158.5
作者：
Finkelstein, JS;Hayes, A;Neer, RM
通讯作者：
Neer, RM
影响因子：
6.2
作者：
Pluijm, Saskia M. F.;Koes, Bart;Steyerberg, Ewout W.
通讯作者：
Steyerberg, Ewout W.
影响因子：
56.9
作者：
Mundy, G;Garrett, R;Gutierrez, G
通讯作者：
Gutierrez, G
影响因子：
1.9
作者：
通讯作者：
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