Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB
AbstractIn 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
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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.
Kang MR, Jo SA, Yoon YD, Park KH, Oh SJ, Yun J, Lee CW, Nam K-H, Kim Y, Han S-B, Yu J, Rho J, Kang JS. Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB. Marine Drugs. 2014; 12(11):5643-5656.Chicago/Turabian Style
Kang, Moo R.; Jo, Sun A.; Yoon, Yeo D.; Park, Ki H.; Oh, Soo J.; Yun, Jieun; Lee, Chang W.; Nam, Ki-Hoan; Kim, Youngsoo; Han, Sang-Bae; Yu, Jiyeon; Rho, Jaerang; Kang, Jong S. 2014. "Agelasine D Suppresses RANKL-Induced Osteoclastogenesis via Down-Regulation of c-Fos, NFATc1 and NF-κB." Mar. Drugs 12, no. 11: 5643-5656.