RRC ID 38603
Author Lee JW, Iwahashi A, Hasegawa S, Yonezawa T, Jeon WB, Cha BY, Nagai K, Woo JT.
Title Coptisine inhibits RANKL-induced NF-κB phosphorylation in osteoclast precursors and suppresses function through the regulation of RANKL and OPG gene expression in osteoblastic cells.
Journal J Nat Med
Abstract 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)(2)D(3) caused significant inhibition of osteoclast formation in a dose-dependent 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)(2)D(3) in osteoblastic cells. Coptisine strongly inhibited RANKL-induced 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.
Volume 66(1)
Pages 8-16
Published 2012-1
DOI 10.1007/s11418-011-0537-7
PMID 21656335
MeSH Animals Berberine / analogs & derivatives* Berberine / pharmacology Bone Density Conservation Agents / pharmacology* Bone Marrow Cells / drug effects* Bone Marrow Cells / metabolism Calcitriol / pharmacology Cell Differentiation / drug effects* Cell Survival / drug effects Cells, Cultured Coculture Techniques Dose-Response Relationship, Drug Gene Expression Regulation / drug effects Male Mice NF-kappa B / metabolism* NFATC Transcription Factors / metabolism Osteoblasts / drug effects* Osteoblasts / metabolism Osteoclasts / drug effects* Osteoclasts / metabolism Osteoprotegerin / genetics Osteoprotegerin / metabolism* Phosphorylation RANK Ligand / genetics RANK Ligand / metabolism* RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Time Factors Transcription Factor RelA / metabolism
IF 1.966
Times Cited 10
Human and Animal Cells