OA-4 Inhibits Osteoclast Formation and Bone Resorption via Suppressing RANKL Induced P38 Signaling Pathway
OA-4 Inhibits Osteoclast Formation and Bone Resorption via Suppressing RANKL Induced P38 Signaling Pathway
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OA-4 通过抑制 RANKL 诱导的 P38 信号通路抑制破骨细胞形成和骨吸收
DOI：
10.2174/09298673113209990190
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发表时间：
2014-02-01
影响因子：
4.1
通讯作者：
Zhu, Z. A.
中科院分区：
文献类型：
--
作者：
Tian, B.;Qin, A.;Zhu, Z. A.
破骨细胞是骨质疏松症、骨关节炎等多种骨科疾病的关键治疗靶点之一。在本研究中，我们合成了一种新型化合物N-(3-(环己基氨基甲酰基)苯基)-1H-吲哚-2-甲酰胺(OA-4)，并研究了OA-4对破骨细胞分化和功能的影响。 OA-4 以剂量依赖性方式显着降低破骨细胞分化和破骨细胞特异性基因表达。此外，OA-4 剂量依赖性地抑制破骨细胞骨吸收。此外，我们发现 OA-4 减弱 RANKL 诱导的 p38 磷酸化，而不影响 JNK 或 NF-kappa B 信号通路。总的来说，我们合成了一种新型化合物 OA-4，它可以通过抑制 p38 信号通路来抑制破骨细胞的形成和功能。
Osteoclasts are one of the key therapeutic targets for a variety of orthopedic diseases such as osteoporosis and osteoarthritis. In this study, we synthesized a novel compound N-(3-(cyclohexylcarbamoyl) phenyl)-1H-indole-2-carboxamide (termed as OA-4) and investigated the effects of OA-4 on the differentiation and function of osteoclasts. OA-4 markedly diminished osteoclast differentiation and osteoclast specific gene expression in a dose-dependent manner. In addition, OA-4 dose-dependently suppressed osteoclastic bone resorption. Furthermore, we found OA-4 attenuated RANKL-induced p38 phosphorylation without affecting JNK or NF-kappa B signaling pathways. Collectively, we synthesized a novel compound OA-4 which can inhibit osteoclast formation and functions via the suppression of p38 signaling pathway.