RRC ID 67939
Author Hasegawa S, Yonezawa T, Ahn JY, Cha BY, Teruya T, Takami M, Yagasaki K, Nagai K, Woo JT.
Title Honokiol inhibits osteoclast differentiation and function in vitro.
Journal Biol Pharm Bull
Abstract Honokiol, a neolignan, is a physiologically active component of kouboku (Magnolia obovata), a herb used in traditional Chinese medicine. This study investigated the effects of honokiol on the differentiation and function of osteoclasts induced by receptor activator of nuclear factor-kappaB ligand (RANKL). Honokiol markedly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of TRAP-positive multinucleated cells in both bone marrow-derived monocytes and RAW264 cells. In experiments to elucidate its mechanism of action, honokiol was found to suppress RANKL-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The RANKL-induced expressions of c-Fos and nuclear factor of activated T cells-c1 (NFATc1), which are crucial transcriptional factors for osteoclastogenesis, were also reduced by treatment with honokiol. Furthermore, honokiol induced disruption of the actin rings in mature osteoclasts (mOCs) without affecting the cell viability and suppressed osteoclastic pit formation on dentin slices. Taken together, these results suggest that honokiol inhibits osteoclast differentiation by suppressing the activation of MAPKs (p38 MAPK, ERK and JNK), decreasing the expressions of c-Fos and NFATc1, and attenuates bone resorption by disrupting the actin rings in mOCs. Therefore, honokiol could prove useful for the treatment of bone diseases associated with excessive bone resorption.
Volume 33(3)
Pages 487-92
Published 2010-1-1
DOI 10.1248/bpb.33.487
PII JST.JSTAGE/bpb/33.487
PMID 20190414
MeSH Acid Phosphatase / metabolism Actins / metabolism Animals Biphenyl Compounds / pharmacology* Bone Density Conservation Agents / pharmacology* Bone Marrow Cells / drug effects* Bone Marrow Cells / metabolism Bone Resorption / metabolism Cell Differentiation / drug effects* Dentin / drug effects Isoenzymes / metabolism Lignans / pharmacology* Magnolia / chemistry* Mice Mitogen-Activated Protein Kinases / metabolism NFATC Transcription Factors / metabolism Osteoclasts / drug effects* Osteoclasts / metabolism Phosphorylation Plant Extracts / pharmacology* Proto-Oncogene Proteins c-fos / metabolism RANK Ligand / metabolism Tartrate-Resistant Acid Phosphatase
IF 1.863
Human and Animal Cells RAW 264(RCB0535)