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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Publisher

Springer US

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DOI

10.1002/hlca.19680510811

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ISSN

1573-4919

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Zinc stimulates osteoblastogenesis and suppresses

Authors: Masayoshi Yamaguchi M Neale Weitzmann
Publish Date: 2011/05/01
Volume: 355, Issue: 1-2, Pages: 179-
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Abstract

Zinc is essential for numerous biochemical pathways in the body and is known to significantly affect the skeleton Zinc has a profound effect on bone turnover promoting bone formation and mineralization but paradoxically inhibiting osteoclastic bone breakdown resorption How zinc regulates these disparate effects on bone cells however is poorly understood We recently characterized several pharmacological and nutritional factors that are likewise endowed with the capacity to promote bone formation and suppress bone resorption and demonstrated that a common centralized mechanism for achieving such actions is through suppression of NFκB activation NFκB is a pathway required for osteoclastogenesis but suppresses osteoblast differentiation In this study we investigated the actions of zinc on NFκB activation in osteoclast and osteoblast precursors in vitro Our data show that zinc suppressed osteoclast differentiation and promoted osteoblast mineralization and did indeed act as a potent NFκB activation antagonist in both osteoclast and osteoblast precursors Importantly zinc antagonized NFκB activation driven by TNFα a potent inflammatory mediator or bone resorption and suppressor of bone formation in vitro and in vivo Zinc further alleviated the suppressive effect of TNFα on Smad activation induced by TGFβ and BMP2 cytokines that play critical roles in osteoblast commitment differentiation and recruitment to sites of bone remodeling In conclusion our data reveal for the first time that a major mechanism by which zinc promotes osteoblastogenesis and suppresses osteoclastogenesis may center on the antagonism of NFκB activation

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