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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-WonIwahashi, AyumiHasegawa, Shin-ichiYonezawa, TakayukiJeon, Won BaeCha, Byung-YoonNagai, KazuoWoo, Je-Tae
DGIST Authors
Jeon, Won Bae
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Animal CellAnimalsBerberineBone Density Conservation AgentsBone Marrow CellBone Marrow CellsCalcitriolCell ActivityCell DifferentiationCell MaturationCell SurvivalCells, CulturedCocultureCoculture TechniquesConcentration ResponseControlled StudyCoptisCoptisineDose-Response Relationship, DrugDrug MechanismDrug StructureGeneGene Expression RegulationImmunoglobulin Enhancer Binding ProteinIn Vitro StudyMacrophageMaleMessenger RNAMetabolic InhibitionMiceMitosis InhibitionMouseNF-Kappa BNFATC Transcription FactorsNFATc1Non-HumanOsteoblastOsteoblastsOsteoclastOsteoclast Differentiation FactorOsteoclastogenesisOsteoclastsOsteoprotegerinOsteoprotegerin GenePhosphorylationProtein ExpressionProtein PhosphorylationRANK LigandRANKLRANKL GeneReceptor Activator of Nuclear Factor Kappa BReverse Transcriptase-Polymerase Chain ReactionRNA, MessengerSignal TransductionStem CellTime FactorsTranscription Factor NFATTranscription 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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Companion Diagnostics and Medical Technology Research Group 1. Journal Articles


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