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Current Topics in Biochemical Research   Volumes    Volume 18 
Synthetic polymethoxyflavonoids, nobiletin and heptamethoxyflavone suppress IL-1-induced osteoclast differentiation and bone resorption
Shigeru Matsumoto, Tsukasa Tominari, Kenta Watanabe, Ayaka Kobayashi, Chiho Matsumoto, Ryota Ichimaru, Shosei Yoshinouchi, Michiko Hirata, Florian M. W. Grundler, Chisato Miyaura, Masaki Inada
Pages: 57 - 63
Number of pages: 7
Current Topics in Biochemical Research
Volume 18 

Copyright © 2017 Research Trends. All rights reserved

Polymethoxyflavonoids (PMFs) are found in citrus fruits, and exert various biological activities. We have previously reported that citrus-derived PMFs showed preventive effects in animal models with bone-resorptive diseases. However, the disadvantage of natural citrus-derived PMFs is the cost associated with high purification. In this study, chemically-synthesized 100% pure PMFs, nobiletin and heptamethoxyflavone, were synthesized, and we examined the effects of synthetic nobiletin (sNobi) and heptamethoxyflavone (sHMF) on osteoclastic bone resorption. In mouse calvarial organ cultures, sNobi and sHMF attenuated the osteoclastic bone resorption elicited by IL-1. Both sNobi and sHMF suppressed the osteoclast formation induced by IL-1 in co-cultures of mouse bone marrow cells and osteoblasts. In osteoblasts, sNobi and sHMF suppressed IL-1-dependent PGE2 production, which is critical for inflammatory bone resorption. These synthetic PMFs also acted on osteoclast precursor cells and suppressed the RANKL-dependent differentiation of macrophages into mature osteoclasts. Synthetic PMFs, sNobi and sHMF, may be useful low-cost compounds that can be used in the prevention and treatment of various bone-related diseases.
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