Honokiol inhibits osteoclast differentiation and function in vitro.
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.
Hasegawa
Shin-Ichi
S
Department of Biological Chemistry, Chubu University, Kasugai, Aichi 487-8501, Japan.
Yonezawa
Takayuki
T
Ahn
Jae-Yong
JY
Cha
Byung-Yoon
BY
Teruya
Toshiaki
T
Takami
Masamichi
M
Yagasaki
Kazumi
K
Nagai
Kazuo
K
Woo
Je-Tae
JT
D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003804:Dentin / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D000498:Allyl Compounds; D010636:Phenols
D000135:Acid Phosphatase; D000199:Actins; D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; D007527:Isoenzymes; D017705:Lignans; D020928:Mitogen-Activated Protein Kinases; D050778:NFATC Transcription Factors; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D000071681:Tartrate-Resistant Acid Phosphatase; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C000605511:Acp5 protein, mouse