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Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

Glass, D.A. and Bialek, P. and Ahn, J.D. and Starbuck, M. and Patel, M.S. and Clevers, J.C. and Taketo, M.M. and Long, F. and McMahon, A.P. and Lang, R.A. and Karsenty, G. (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Developmental cell, 8(5), 751-764. ISSN 15345807. doi: 10.1016/j.devcel.2005.02.017.

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Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.

Item Type:Article
Additional Information:doi: 10.1016/j.devcel.2005.02.017
Institutes:Hubrecht Instituut
ID Code:3612
Deposited On:13 Feb 2009 17:14
Last Modified:10 Dec 2009 13:14

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