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OA10 Is a Novel p38alpha Mitogen‐Activated Protein Kinase Inhibitor That Suppresses Osteoclast Differentiation and Bone Resorption
Author(s) -
Jiang T.,
Qin A.,
Shao Z.Y.,
Tian B.,
Zhai Z.J.,
Li H.W.,
Zhu Z.A.,
Dai K.R.,
Ming H. Zheng,
Yu Y.P.,
Jiang Q.
Publication year - 2014
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24744
Subject(s) - bone resorption , osteoclast , cathepsin k , chemistry , rankl , p38 mitogen activated protein kinases , tartrate resistant acid phosphatase , osteolysis , microbiology and biotechnology , signal transduction , cancer research , receptor , protein kinase a , phosphorylation , pharmacology , biochemistry , endocrinology , biology , medicine , activator (genetics) , surgery
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. J. Cell. Biochem. 115: 959–966, 2014. © 2013 Wiley Periodicals, Inc.