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

Authors
  • 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
Type
Published Article
Journal
Journal of Cellular Biochemistry
Publisher
Wiley (John Wiley & Sons)
Publication Date
May 01, 2014
Volume
115
Issue
5
Pages
959–966
Identifiers
DOI: 10.1002/jcb.24744
PMID: 24357524
Source
Medline
Keywords
License
Unknown

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.

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