BPB Reports

Paper Details

BPB Reports
Vol. 2 No. 1 p.1-6 2019
Regular Article
Structure-Activity Relationship of Anthocyanidins as an Inhibitory Effect on Osteoclast Differentiation
  • Masaki Inada (Cooperative Major of Advanced Health Science, Tokyo University of Agriculture and Technology / Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology / Institute of Global Innovation Research, Tokyo University of Agriculture and Technology / m-inada@cc.tuat.ac.jp)
Narumi Hirata 1) , Tsukasa Tominari 2) , Ryota Ichimaru 1) , Keita Taniguchi 2) , Chiho Matsumoto 2) , Kenta Watanabe 3) , Michiko Hirata 2) , Sihui Ma 4) , Katsuhiko Suzuki 5) , Florian M.W. Grundler 3) 6) , Chisato Miyaura 1) 2) 3) , Masaki Inada 1) 2) 3)
1) Cooperative Major of Advanced Health Science, Tokyo University of Agriculture and Technology , 2) Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology , 3) Institute of Global Innovation Research, Tokyo University of Agriculture and Technology , 4) Graduate School of Sport Sciences, Waseda University , 5) Faculty of Sport Sciences, Waseda University , 6) Institute of Crop Science and Resource Conservation, University of Bonn
Received: December 26, 2018;   Accepted: January 17, 2019;   Released: March 06, 2019
Keywords: anthocyanidins, osteoclast, bone resorption, lipopolysaccharide
Abstracts

Anthocyanins are plant-derived pigments, and their aglycons are called anthocyanidin. Anthocyanidins have shown to exhibit various biological functions, such as anti-oxidant effects. However, their structure-activity relationship in bone tissue is not known. In this study, we examined the effects of three anthocyanidins, delphinidin, cyanidin and pelargonidin, on osteoclast differentiation and bone resorption to elucidate the structure-activity relationship. Anthocyanidins suppressed both IL-1 and LPS induced osteoclast differentiation in cocultures of bone marrow cells and primary osteoblasts, and bone resorbing activity in calvarial organ cultures. In osteoblasts, anthocyanidins inhibited prostaglandin (PG) E2 production via the downregulation of membrane-bound PGE synthase (mPGES)-1, leading to the suppression of PGE2-mediated receptor-activator of nuclear factorkappa B (NF-κB) ligand (RANKL) expression. In osteoclasts, anthocyanidins inhibited RANKL-induced osteoclast differentiation through the downregulation of osteoclast differentiation marker genes, nuclear factor of activated T-cells 1 (NFATc1), cathepsin K and tartrate-resistant acid phosphatase (TRAP). We further found that anthocyanidins suppressed the inhibitor of NF-κB kinase (IKK) activity in vitro assay, a signal component of NF-κB pathway, suggesting IKK was a novel target molecule of anthocyanidins. We found that delphinidin exerted the most potent inhibitory activity in these experiments, compared with cyanidin and pelargonidin. Anthocyanidins exhibits inhibitory activity in bone resorption, which may depend on the number of hydroxide residues.