OA-4 inhibits osteoclast formation and bone resorption via suppressing RANKL induced P38 signaling pathway

• Published in: Current medicinal chemistry Vol. 21; no. 5; p. 641
• Main Authors: Tian, B, Qin, A, Shao, Z Y, Jiang, T, Zhai, Z J, Li, H W, Tang, T T, Jiang, Q, Dai, K R, Zheng, M H, Yu, Y P, Zhu, Z A
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.02.2014
• Subjects: Animals; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Matrix - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Gene Expression Regulation - drug effects; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Macrophages - cytology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Monocytes - cytology; Monocytes - metabolism; Osteoclasts - cytology; Osteoclasts - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; RANK Ligand - pharmacology; Signal Transduction - drug effects
• ISSN: 1875-533X
• DOI: 10.2174/09298673113209990190

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.