Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.

Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalli...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jochen Schulze, Sebastian Seitz, Hiroaki Saito, Michael Schneebauer, Robert P Marshall, Anke Baranowsky, Bjoern Busse, Arndt F Schilling, Felix W Friedrich, Joachim Albers, Alexander S Spiro, Jozef Zustin, Thomas Streichert, Kristina Ellwanger, Christof Niehrs, Michael Amling, Roland Baron, Thorsten Schinke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c6c239f6c7a4a1fab9fd5114bc3cb72
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9c6c239f6c7a4a1fab9fd5114bc3cb72
record_format	dspace
spelling	oai:doaj.org-article:9c6c239f6c7a4a1fab9fd5114bc3cb722021-12-02T20:22:06ZNegative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.1932-620310.1371/journal.pone.0010309https://doaj.org/article/9c6c239f6c7a4a1fab9fd5114bc3cb722010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20436912/?tool=EBIhttps://doaj.org/toc/1932-6203Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders.Jochen SchulzeSebastian SeitzHiroaki SaitoMichael SchneebauerRobert P MarshallAnke BaranowskyBjoern BusseArndt F SchillingFelix W FriedrichJoachim AlbersAlexander S SpiroJozef ZustinThomas StreichertKristina EllwangerChristof NiehrsMichael AmlingRoland BaronThorsten SchinkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10309 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jochen Schulze Sebastian Seitz Hiroaki Saito Michael Schneebauer Robert P Marshall Anke Baranowsky Bjoern Busse Arndt F Schilling Felix W Friedrich Joachim Albers Alexander S Spiro Jozef Zustin Thomas Streichert Kristina Ellwanger Christof Niehrs Michael Amling Roland Baron Thorsten Schinke Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
description	Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders.
format	article
author	Jochen Schulze Sebastian Seitz Hiroaki Saito Michael Schneebauer Robert P Marshall Anke Baranowsky Bjoern Busse Arndt F Schilling Felix W Friedrich Joachim Albers Alexander S Spiro Jozef Zustin Thomas Streichert Kristina Ellwanger Christof Niehrs Michael Amling Roland Baron Thorsten Schinke
author_facet	Jochen Schulze Sebastian Seitz Hiroaki Saito Michael Schneebauer Robert P Marshall Anke Baranowsky Bjoern Busse Arndt F Schilling Felix W Friedrich Joachim Albers Alexander S Spiro Jozef Zustin Thomas Streichert Kristina Ellwanger Christof Niehrs Michael Amling Roland Baron Thorsten Schinke
author_sort	Jochen Schulze
title	Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
title_short	Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
title_full	Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
title_fullStr	Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
title_full_unstemmed	Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.
title_sort	negative regulation of bone formation by the transmembrane wnt antagonist kremen-2.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/9c6c239f6c7a4a1fab9fd5114bc3cb72
work_keys_str_mv	AT jochenschulze negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT sebastianseitz negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT hiroakisaito negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT michaelschneebauer negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT robertpmarshall negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT ankebaranowsky negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT bjoernbusse negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT arndtfschilling negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT felixwfriedrich negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT joachimalbers negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT alexandersspiro negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT jozefzustin negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT thomasstreichert negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT kristinaellwanger negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT christofniehrs negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT michaelamling negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT rolandbaron negativeregulationofboneformationbythetransmembranewntantagonistkremen2 AT thorstenschinke negativeregulationofboneformationbythetransmembranewntantagonistkremen2
_version_	1718374121386016768

Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.

Ejemplares similares