{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:36:56Z","timestamp":1771634216387,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T00:00:00Z","timestamp":1416787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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 \u03baB 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-\u03baB 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-\u03baB and ERK. Our results also suggest that AD might be a potential therapeutic agent for prevention and treatment of osteoporosis.<\/jats:p>","DOI":"10.3390\/md12115643","type":"journal-article","created":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T11:06:32Z","timestamp":1416827192000},"page":"5643-5656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-\u03baB"],"prefix":"10.3390","volume":"12","author":[{"given":"Moo","family":"Kang","sequence":"first","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun","family":"Jo","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeo","family":"Yoon","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo","family":"Oh","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieun","family":"Yun","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Hoan","family":"Nam","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 52 Naesudongro, Cheongju 361-763, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Bae","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 52 Naesudongro, Cheongju 361-763, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyeon","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, Chungnam National University, 99 Daehakro, Daejeon 305-764, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaerang","family":"Rho","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Molecular Biology, Chungnam National University, 99 Daehakro, Daejeon 305-764, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong","family":"Kang","sequence":"additional","affiliation":[{"name":"Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology,  30 Yeongudanjiro, Cheongju 363-883, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S1534-5807(02)00157-0","article-title":"Reaching a genetic and molecular understanding of skeletal development","volume":"2","author":"Karsenty","year":"2002","journal-title":"Dev. 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