OA10 Is a Novel p38alpha Mitogen‐Activated Protein Kinase Inhibitor That Suppresses Osteoclast Differentiation and Bone Resorption
OA10 Is a Novel p38alpha Mitogen‐Activated Protein Kinase Inhibitor That Suppresses Osteoclast Differentiation and Bone Resorption
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DOI：
10.1002/jcb.24744
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发表时间：
2014-05
影响因子：
4
通讯作者：
T. Jiang;A. Qin;An Qin;Zhiyong Shao;B. Tian;Z. Zhai;Huihua Li;Z. Zhu;K. Dai;H. Z. Ming;Yongping Yu;Q. Jiang
中科院分区：
文献类型：
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作者：
T. Jiang;A. Qin;An Qin;Zhiyong Shao;B. Tian;Z. Zhai;Huihua Li;Z. Zhu;K. Dai;H. Z. Ming;Yongping Yu;Q. Jiang
为了寻找可能治疗骨质疏松的抗骨吸收药物，我们合成了一种新型化合物Tert - butyl - 4 - （3 - [1H -吲哚- 2 - carboxamido]苯甲酰）哌嗪- 1 -羧酸酯（OA10），并发现OA10能够以剂量依赖的方式抑制RANKL介导的破骨细胞形成和破骨细胞骨吸收。OA10抑制破骨细胞特异性基因表达，包括酒石酸盐抗性酸性磷酸酶、组织蛋白酶K受体和降钙素受体，这一事实进一步支持了这种生物学效应。进一步的分子机制研究表明，OA10抑制p38磷酸化，抑制c - fos和NFATc1的表达，而不影响NF - κB或JNK信号通路。综上所述，本研究表明OA10可以通过抑制p38‐c‐Fos‐NFATc1级联来抑制破骨细胞的发生。OA10可能成为一种治疗破骨细胞相关溶骨疾病的药物。j .细胞。中国生物医学工程学报，2014,31(2):559 - 566。©2013 Wiley期刊公司
In search of anti‐bone resorbing agents for the potential treatment of osteoporosis, we synthesized a novel compound Tert‐butyl 4‐(3‐[1H‐indole‐2‐carboxamido]benzoyl)piperazine‐1‐carboxylate (OA10) and found that OA10 is capable of inhibiting RANKL‐mediated osteoclast formation and osteoclastic bone resorption in a dose‐dependent manner. This biological effect is further supported by the fact that OA10 suppressed osteoclastic‐specific gene expression, including tartrate‐resistant acid phosphatase, cathepsin K receptor, and calcitonin receptor. Further molecular mechanism investigation revealed OA10 inhibited p38 phosphorylation, suppressed c‐fos and NFATc1 expression without affecting NF‐κB or JNK signaling pathways. Taken together, this study suggested that OA10 can inhibit osteoclastogenesis by suppressing p38‐c‐Fos‐NFATc1 cascade. OA10 may be developed as a therapeutic drug for osteoclast‐related osteolytic diseases. J. Cell. Biochem. 115: 959–966, 2014. © 2013 Wiley Periodicals, Inc.