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Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin

Although Wnt signaling is considered a key regulatory pathway for bone formation, inactivation of β-catenin in osteoblasts does not affect their activity but rather causes increased osteoclastogenesis due to insufficient production of osteoprotegerin (Opg). By monitoring the expression pattern of al...

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Autores principales: Albers, Joachim, Keller, Johannes, Baranowsky, Anke, Beil, Frank Timo, Catala-Lehnen, Philip, Schulze, Jochen, Amling, Michael, Schinke, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575535/
https://www.ncbi.nlm.nih.gov/pubmed/23401003
http://dx.doi.org/10.1083/jcb.201207142
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author Albers, Joachim
Keller, Johannes
Baranowsky, Anke
Beil, Frank Timo
Catala-Lehnen, Philip
Schulze, Jochen
Amling, Michael
Schinke, Thorsten
author_facet Albers, Joachim
Keller, Johannes
Baranowsky, Anke
Beil, Frank Timo
Catala-Lehnen, Philip
Schulze, Jochen
Amling, Michael
Schinke, Thorsten
author_sort Albers, Joachim
collection PubMed
description Although Wnt signaling is considered a key regulatory pathway for bone formation, inactivation of β-catenin in osteoblasts does not affect their activity but rather causes increased osteoclastogenesis due to insufficient production of osteoprotegerin (Opg). By monitoring the expression pattern of all known genes encoding Wnt receptors in mouse tissues and bone cells we identified Frizzled 8 (Fzd8) as a candidate regulator of bone remodeling. Fzd8-deficient mice displayed osteopenia with normal bone formation and increased osteoclastogenesis, but this phenotype was not associated with impaired Wnt signaling or Opg production by osteoblasts. The deduced direct negative influence of canonical Wnt signaling on osteoclastogenesis was confirmed in vitro and through the generation of mice lacking β-catenin in the osteoclast lineage. Here, we observed increased bone resorption despite normal Opg production and a resistance to the anti-osteoclastogenic effect of Wnt3a. These results demonstrate that Fzd8 and β-catenin negatively regulate osteoclast differentiation independent of osteoblasts and that canonical Wnt signaling controls bone resorption by two different mechanisms.
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spelling pubmed-35755352013-08-18 Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin Albers, Joachim Keller, Johannes Baranowsky, Anke Beil, Frank Timo Catala-Lehnen, Philip Schulze, Jochen Amling, Michael Schinke, Thorsten J Cell Biol Research Articles Although Wnt signaling is considered a key regulatory pathway for bone formation, inactivation of β-catenin in osteoblasts does not affect their activity but rather causes increased osteoclastogenesis due to insufficient production of osteoprotegerin (Opg). By monitoring the expression pattern of all known genes encoding Wnt receptors in mouse tissues and bone cells we identified Frizzled 8 (Fzd8) as a candidate regulator of bone remodeling. Fzd8-deficient mice displayed osteopenia with normal bone formation and increased osteoclastogenesis, but this phenotype was not associated with impaired Wnt signaling or Opg production by osteoblasts. The deduced direct negative influence of canonical Wnt signaling on osteoclastogenesis was confirmed in vitro and through the generation of mice lacking β-catenin in the osteoclast lineage. Here, we observed increased bone resorption despite normal Opg production and a resistance to the anti-osteoclastogenic effect of Wnt3a. These results demonstrate that Fzd8 and β-catenin negatively regulate osteoclast differentiation independent of osteoblasts and that canonical Wnt signaling controls bone resorption by two different mechanisms. The Rockefeller University Press 2013-02-18 /pmc/articles/PMC3575535/ /pubmed/23401003 http://dx.doi.org/10.1083/jcb.201207142 Text en © 2013 Albers et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Albers, Joachim
Keller, Johannes
Baranowsky, Anke
Beil, Frank Timo
Catala-Lehnen, Philip
Schulze, Jochen
Amling, Michael
Schinke, Thorsten
Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title_full Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title_fullStr Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title_full_unstemmed Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title_short Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
title_sort canonical wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575535/
https://www.ncbi.nlm.nih.gov/pubmed/23401003
http://dx.doi.org/10.1083/jcb.201207142
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