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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / chemistry
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Benzamides / pharmacology*
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects*
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Bone Matrix / metabolism*
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Cell Differentiation / drug effects
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Cells, Cultured
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Gene Expression Regulation / drug effects
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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Macrophages / cytology
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Macrophages / metabolism
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Mice
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Mice, Inbred C57BL
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Monocytes / cytology
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Monocytes / metabolism
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Osteoclasts / cytology*
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Osteoclasts / metabolism
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Phosphorylation / drug effects
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RANK Ligand / pharmacology*
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Signal Transduction / drug effects*
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p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
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Benzamides
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Indoles
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N-(3-(cyclohexylcarbamoyl)phenyl)-1H-indole-2-carboxamide
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RANK Ligand
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p38 Mitogen-Activated Protein Kinases