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Citrus Limonoid Nomilin Inhibits Osteoclastogenesis in Vitro by Suppression of NFATc1 and MAPK Signaling Pathways

Citrus Limonoid Nomilin Inhibits Osteoclastogenesis in Vitro by Suppression of NFATc1 and MAPK Signaling Pathways

Yoshifumi Kimira, Yuri Taniuchi, Sachie Nakatani, Yuusuke Sekiguchi, Hyoun Ju Kim, Jun Shimizu, Midori Ebata, Masahiro Wada, Akiyo Matsumoto, Hiroshi Mano

Phytomedicine. 2015 Nov 15;22(12):1120-4.

PMID: 26547535

Abstract:

Background:
Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.
Purpose:
To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.
Study design:
Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.
Methods:
Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.
Results:
Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.
Conclusion:
This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1063770	Nomilin		1063-77-0	Price

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