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Coptisine inhibits RANKL-induced NF-kappa B phosphorylation in osteoclast precursors and suppresses function through the regulation of RANKL and OPG gene expression in osteoblastic cells
- Coptisine inhibits RANKL-induced NF-kappa B phosphorylation in osteoclast precursors and suppresses function through the regulation of RANKL and OPG gene expression in osteoblastic cells
- Lee, Ji-Won; Iwahashi, Ayumi; Hasegawa, Shin-ichi; Yonezawa, Takayuki; Jeon, Won Bae; Cha, Byung-Yoon; Nagai, Kazuo; Woo, Je-Tae
- DGIST Authors
- Jeon, Won Bae
- Issue Date
- Journal of Natural Medicines, 66(1), 8-16
- Article Type
- Animal Cell; Animals; Berberine; Bone Density Conservation Agents; Bone Marrow Cell; Bone Marrow Cells; Calcitriol; Cell Activity; Cell Differentiation; Cell Maturation; Cell Survival; Cells, Cultured; Coculture; Coculture Techniques; Concentration Response; Controlled Study; Coptis; Coptisine; Dose-Response Relationship, Drug; Drug Mechanism; Drug Structure; Gene; Gene Expression Regulation; Immunoglobulin Enhancer Binding Protein; In Vitro Study; Macrophage; Male; Messenger RNA; Metabolic Inhibition; Mice; Mitosis Inhibition; Mouse; NF-Kappa B; NFATC Transcription Factors; NFATc1; Non-Human; Osteoblast; Osteoblasts; Osteoclast; Osteoclast Differentiation Factor; Osteoclastogenesis; Osteoclasts; Osteoprotegerin; Osteoprotegerin Gene; Phosphorylation; Protein Expression; Protein Phosphorylation; RANK Ligand; RANKL; RANKL Gene; Receptor Activator of Nuclear Factor Kappa B; Reverse Transcriptase-Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Stem Cell; Time Factors; Transcription Factor NFAT; Transcription Factor Rela
- Excessive receptor activator of NF-κB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. The downregulation of RANKL expression and its downstream signals may be an effective therapeutic approach to the treatment of bone loss diseases such as osteoporosis. Here, we found that coptisine, one of the isoquinoline alkaloids from Coptidis Rhizoma, exhibited inhibitory effects on osteoclastogenesis in vitro. Although coptisine has been studied for its antipyretic, antiphotooxidative, dampness dispelling, antidote, antinociceptive, and anti-inflammatory activities in vitro and in vivo, its effects on osteoclastogenesis have not been investigated. Therefore, we evaluated the effects of coptisine on osteoblastic cells as well as osteoclast precursors for osteoclastogenesis in vitro. The addition of coptisine to cocultures of mouse bone marrow cells and primary osteoblastic cells with 10 -8 M 1α,25(OH) 2D 3 caused significant inhibition of osteoclast formation in a dosedependent manner. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that coptisine inhibited RANKL gene expression and stimulated the osteoprotegerin gene expression induced by 1α,25(OH) 2D 3 in osteoblastic cells. Coptisine strongly inhibited RANKLinduced osteoclast formation when added during the early stage of bone marrow macrophage (BMM) cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, coptisine inhibited NF-κB p65 phosphorylations, which are regulated in response to RANKL in BMMs. Coptisine also inhibited the RANKL-induced expression of NFATc1, which is a key transcription factor. In addition, 10 μM coptisine significantly inhibited both the survival of mature osteoclasts and their pit-forming activity in cocultures. Thus, coptisine has potential for the treatment or prevention of several bone diseases characterized by excessive bone destruction. © The Japanese Society of Pharmacognosy and Springer 2011.
- Springer Tokyo
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