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Mar. Drugs 2014, 12(11), 5643-5656; doi:10.3390/md12115643

Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB

1
Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, Korea
2
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, Korea
3
College of Pharmacy, Chungbuk National University, 52 Naesudongro, Cheongju 361-763, Korea
4
Department of Microbiology & Molecular Biology, Chungnam National University, 99 Daehakro, Daejeon 305-764, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 August 2014 / Revised: 31 October 2014 / Accepted: 12 November 2014 / Published: 24 November 2014
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Abstract

In the present study, we investigated the effect of agelasine D (AD) on osteoclastogenesis. Treatment of bone marrow macrophages (BMMs) with receptor activator of nuclear factor κB ligand (RANKL) resulted in a differentiation of BMMs into osteoclasts as evidenced by generation of tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated cells and formation of pits in calcium phosphate-coated plates. However, RANKL-induced osteoclastogenesis was significantly suppressed by AD treatment. We also confirmed the increased mRNA and protein expression of osteoclastic markers, such as TRAP, cathepsin K and matrix metalloproteinase-9, during RANKL-induced osteoclast differentiation and this was down-regulated by AD treatment. Moreover, AD treatment significantly suppressed RANKL-induced mRNA expression of DC-STAMP and OC-STAMP and cell fusion of TRAP-positive mononuclear osteoclast precursors. In addition, AD suppressed RANKL-induced expression of transcription factors, c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important transcription factors involved in differentiation of BMMs into osteoclasts. Furthermore, RANKL-induced phosphorylation of extracellular signal-related kinase (ERK) and activation of NF-κB were also inhibited by AD treatment. Collectively, these results suggest that AD inhibits RANKL-induced osteoclastogenesis by down-regulation of multiple signaling pathways involving c-Fos, NFATc1, NF-κB and ERK. Our results also suggest that AD might be a potential therapeutic agent for prevention and treatment of osteoporosis. View Full-Text
Keywords: agelasine D; osteoclastogenesis; c-Fos; NF-ATc1; NF-κB agelasine D; osteoclastogenesis; c-Fos; NF-ATc1; NF-κB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kang, M.R.; Jo, S.A.; Yoon, Y.D.; Park, K.H.; Oh, S.J.; Yun, J.; Lee, C.W.; Nam, K.-H.; Kim, Y.; Han, S.-B.; Yu, J.; Rho, J.; Kang, J.S. Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB. Mar. Drugs 2014, 12, 5643-5656.

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