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Palmatine Attenuates Osteoclast Differentiation and Function through Inhibition of Receptor Activator of Nuclear Factor-kappa B Ligand Expression in Osteoblast Cells

Title
Palmatine Attenuates Osteoclast Differentiation and Function through Inhibition of Receptor Activator of Nuclear Factor-kappa B Ligand Expression in Osteoblast Cells
Authors
Lee, Ji-WonMase, NaomiYonezawa, TakayukiSeo, Hwa-JeongJeon, Won BaeCha, Byung YoonNagai, KazuoWoo, Je-Tae
DGIST Authors
Jeon, Won Bae
Issue Date
2010-10
Citation
Biological & Pharmaceutical Bulletin, 33(10), 1733-1739
Type
Article
Article Type
Article
Keywords
Necrosis-Factor ReceptorBone-ResorptionResorbing OsteoclastsBerberineCalcitoninAlkaloidsBindingKinasePhotooxidationCytoskeleton
ISSN
0918-6158
Abstract
Osteoclasts are the only cell type capable of resorbing mineralized bone, and they act under the control of numerous cytokines produced by supporting cells such as osteoblasts and stromal cells. Among cytokines, receptor activator of nuclear factor-κB ligand (RANKL) was found to be a key osteoclastogenetic molecule that directly binds to its cognate receptor, RANK, on osteoclast precursor cells. In turn, RANKL, which is an essential factor for differentiation and activation of osteoclasts, is one of the major targets of anti-resorptive agents. In this study, we found that palmatine, an isoquinoline alkaloid originally isolated from Coptis chinensis, had an inhibitory effect on osteoclast differentiation and function in vitro. Palmatine inhibited osteoclast formation in the co-culture system with mouse bone marrow cells (BMC) and osteoblasts in the presence of 10 nM 1α,25-(OH)2D3. Palmatine did not affect osteoclast formation induced by RANKL in the BMC cultures. Reverse-transcription polymerase chain reaction (RT-PCR) analysis showed that palmatine significantly inhibited the expression of 1α,25-(OH)2D3-induced expression of RANKL mRNAs in stromal cells without loss of cell viability. Moreover, palmatine suppressed resorption pit formation by mature osteoclasts on dentin slices and induced disruption of actin ring formation in mature osteoclasts with an impact on cell viability. Taken together, these results suggest that palmatine attenuates osteoclast differentiation through inhibition of RANKL expression in osteoblast cells, and its inhibitory effect on bone resorption is due to its disruptive effect on actin rings in mature osteoclasts. Therefore, palmatine might be an ideal candidate as an anti-resorptive agent for the prevention and treatment of bone disorders such as osteoporosis. © 2010 Pharmaceutical Society of Japan.
URI
http://hdl.handle.net/20.500.11750/6499
DOI
10.1248/bpb.33.1733
Publisher
PHARMACEUTICAL SOC JAPAN
Related Researcher
Files:
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Collection:
Companion Diagnostics and Medical Technology Research Group1. Journal Articles


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