Current Medicinal Chemistry

Author(s): B. Tian, A. Qin, Z.Y. Shao, T. Jiang, Z.J. Zhai, H.W. Li, T.T. Tang, Q. Jiang, K.R. Dai, M.H. Zheng, Y.P. Yu and Z.A. Zhu

DOI: 10.2174/09298673113209990190

OA-4 Inhibits Osteoclast Formation and Bone Resorption via Suppressing RANKL Induced P38 Signaling Pathway

Page: [641 - 649] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

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-κB signaling pathways. Collectively, we synthesized a novel compound OA-4 which can inhibit osteoclast formation and functions via the suppression of p38 signaling pathway.

Keywords: OA-4, osteoclast formation, osteoclastic bone resorption, osteoporosis, P38 signaling pathway.