Abstract
Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent.
Keywords:
5,6-dehydrokawain; Alpinia zerumbet; MC3T3-E1; osteoblast; osteoporosis.
MeSH terms
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Alkaline Phosphatase / genetics
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Alkaline Phosphatase / metabolism
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Alpinia / chemistry*
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Animals
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Cell Differentiation / drug effects*
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Cell Line
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Cell Proliferation / drug effects
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Core Binding Factor Alpha 1 Subunit / agonists
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Core Binding Factor Alpha 1 Subunit / genetics
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Core Binding Factor Alpha 1 Subunit / metabolism
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Gene Expression Regulation
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Homeodomain Proteins / agonists
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism
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Mice
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Osteoblasts / cytology
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Osteoblasts / drug effects*
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Osteoblasts / metabolism
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Osteogenesis / drug effects*
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Osteogenesis / genetics
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Plant Extracts / chemistry
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Pyrones / isolation & purification
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Pyrones / pharmacology*
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RNA, Messenger / agonists
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rhizome / chemistry
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Sp7 Transcription Factor
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Transcription Factors / agonists
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Transcription Factors / genetics
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Transcription Factors / metabolism
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Core Binding Factor Alpha 1 Subunit
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Dlx5 protein, mouse
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Homeodomain Proteins
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Plant Extracts
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Pyrones
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RNA, Messenger
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Runx2 protein, mouse
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Sp7 Transcription Factor
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Sp7 protein, mouse
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Transcription Factors
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5,6-dehydrokawain
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7,8-dihydro-5,6-dehydrokawain
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p38 Mitogen-Activated Protein Kinases
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Alkaline Phosphatase