RRC ID 18931
Author Lee JW, Mase N, Yonezawa T, Seo HJ, Jeon WB, Cha BY, Nagai K, Woo JT.
Title Palmatine attenuates osteoclast differentiation and function through inhibition of receptor activator of nuclear factor-κb ligand expression in osteoblast cells.
Journal Biol Pharm Bull
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)(2)D(3). 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)(2)D(3)-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.
Volume 33(10)
Pages 1733-9
Published 2010-1-1
DOI 10.1248/bpb.33.1733
PII JST.JSTAGE/bpb/33.1733
PMID 20930384
MeSH Actins / metabolism Animals Berberine Alkaloids / pharmacology* Berberine Alkaloids / therapeutic use Bone Density Conservation Agents / pharmacology* Bone Density Conservation Agents / therapeutic use Bone Resorption / physiopathology Bone Resorption / prevention & control* Cell Differentiation / drug effects* Cell Survival / drug effects Coptis / chemistry Dentin / metabolism Mice Osteoclasts / cytology Osteoclasts / drug effects* Osteoporosis / drug therapy Osteoporosis / prevention & control Phytotherapy Plant Extracts / pharmacology* Plant Extracts / therapeutic use RANK Ligand / antagonists & inhibitors* RANK Ligand / genetics RNA, Messenger / metabolism Stromal Cells / metabolism
IF 1.863
Times Cited 17
Human and Animal Cells RAW 264(RCB0535) ST2(RCB0224)