Delphinidin, one of the major anthocyanidins, prevents bone loss through the inhibition of excessive osteoclastogenesis in osteoporosis model mice.
Anthocyanins, one of the flavonoid subtypes, are a large family of water-soluble phytopigments and have a wide range of health-promoting benefits. Recently, an anthocyanin-rich compound from blueberries was reported to possess protective property against bone loss in ovariectomized (OVX) animal models. However, the active ingredients in the anthocyanin compound have not been identified. Here we show that delphinidin, one of the major anthocyanidins in berries, is a potent active ingredient in anti-osteoporotic bone resorption through the suppression of osteoclast formation. In vitro examinations revealed that delphinidin treatment markedly inhibited the differentiation of RAW264.7 cells into osteoclasts compared with other anthocyanidins, cyanidin and peonidin. Oral administration of delphinidin significantly prevented bone loss in both RANKL-induced osteoporosis model mice and OVX model mice. We further provide evidence that delphinidin suppressed the activity of NF-κB, c-fos, and Nfatc1, master transcriptional factors for osteoclastogenesis. These results strongly suggest that delphinidin is the most potent inhibitor of osteoclast differentiation and will be an effective agent for preventing bone loss in postmenopausal osteoporosis.
Laboratory of Genomics and Proteomics, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan; Biobank Omics Unit, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan.
Sawako
S
Moriwaki
Department of Pharmacology, School of Dentistry, Showa University, Tokyo, Japan.
Keiko
K
Suzuki
Laboratory of Genomics and Proteomics, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan.
Masashi
M
Muramatsu
Nihon Seiyaku Kogyo, Co., Ltd., Aichi, Japan.
Atsushi
A
Nomura
Nihon Seiyaku Kogyo, Co., Ltd., Aichi, Japan.
Fumihide
F
Inoue
Department of Oral Bacteriology, Division of Oral Infections and Health Sciences, Asahi University School of Dentistry, Gifu, Japan.
Takeshi
T
Into
Department of Oral Growth and Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Yuji
Y
Yoshiko
Laboratory of Genomics and Proteomics, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan; Biobank Omics Unit, National Center for Geriatrics and Gerontology (NCGG), Aichi, Japan.
Shumpei
S
Niida
D000284:Administration, Oral; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D029798:Blueberry Plants / Q000737:chemistry*; D001862:Bone Resorption / Q000517:prevention & control*; D002460:Cell Line; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055114:X-Ray Microtomography
D000872:Anthocyanins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; C017185:delphinidin