OA10 is a novel p38alpha mitogen-activated protein kinase inhibitor that suppresses osteoclast differentiation and bone resorption

T. Jiang, A. Qin, Z. Shao, B. Tian, Z. Zhai, H. Li, Z. Zhu, K. Dai, Ming Ming, Y. Yu, Q. Jiang

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    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. © 2013 Wiley Periodicals, Inc.
    Original languageEnglish
    Pages (from-to)959-966
    JournalJournal of Cellular Biochemistry
    Volume115
    Issue number5
    Early online date4 Mar 2013
    DOIs
    Publication statusPublished - May 2014

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