Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB
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...
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MDPI AG
2014-11-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/12/11/5643 |
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| author | Moo Rim Kang Sun Ah Jo Yeo Dae Yoon Ki Hwan Park Soo Jin Oh Jieun Yun Chang Woo Lee Ki-Hoan Nam Youngsoo Kim Sang-Bae Han Jiyeon Yu Jaerang Rho Jong Soon Kang |
| author_facet | Moo Rim Kang Sun Ah Jo Yeo Dae Yoon Ki Hwan Park Soo Jin Oh Jieun Yun Chang Woo Lee Ki-Hoan Nam Youngsoo Kim Sang-Bae Han Jiyeon Yu Jaerang Rho Jong Soon Kang |
| author_sort | Moo Rim Kang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T08:08:19Z |
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| last_indexed | 2024-12-10T08:08:19Z |
| publishDate | 2014-11-01 |
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| series | Marine Drugs |
| spelling | doaj.art-f0e4146737b84b118676b5e3c472e12a2022-12-22T01:56:38ZengMDPI AGMarine Drugs1660-33972014-11-0112115643565610.3390/md12115643md12115643Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κBMoo Rim Kang0Sun Ah Jo1Yeo Dae Yoon2Ki Hwan Park3Soo Jin Oh4Jieun Yun5Chang Woo Lee6Ki-Hoan Nam7Youngsoo Kim8Sang-Bae Han9Jiyeon Yu10Jaerang Rho11Jong Soon Kang12Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaLaboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaCollege of Pharmacy, Chungbuk National University, 52 Naesudongro, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, 52 Naesudongro, Cheongju 361-763, KoreaDepartment of Microbiology & Molecular Biology, Chungnam National University, 99 Daehakro, Daejeon 305-764, KoreaDepartment of Microbiology & Molecular Biology, Chungnam National University, 99 Daehakro, Daejeon 305-764, KoreaBio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanjiro, Cheongju 363-883, KoreaIn 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.http://www.mdpi.com/1660-3397/12/11/5643agelasine Dosteoclastogenesisc-FosNF-ATc1NF-κB |
| spellingShingle | Moo Rim Kang Sun Ah Jo Yeo Dae Yoon Ki Hwan Park Soo Jin Oh Jieun Yun Chang Woo Lee Ki-Hoan Nam Youngsoo Kim Sang-Bae Han Jiyeon Yu Jaerang Rho Jong Soon Kang Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB Marine Drugs agelasine D osteoclastogenesis c-Fos NF-ATc1 NF-κB |
| title | Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB |
| title_full | Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB |
| title_fullStr | Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB |
| title_full_unstemmed | Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB |
| title_short | Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB |
| title_sort | agelasine d suppresses rankl induced osteoclastogenesis via down regulation of c fos nfatc1 and nf κb |
| topic | agelasine D osteoclastogenesis c-Fos NF-ATc1 NF-κB |
| url | http://www.mdpi.com/1660-3397/12/11/5643 |
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