PortalPublikationenWnt1 is an Lrp5-independent bone-anabolic Wnt ligand

Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand

Standard

Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand. / Luther, Julia; Yorgan, Timur Alexander; Rolvien, Tim; Ulsamer, Lorenz; Koehne, Till; Liao, Nannan; Keller, Daniela; Vollersen, Nele; Teufel, Stefan; Neven, Mona; Peters, Stephanie; Schweizer, Michaela; Trumpp, Andreas; Rosigkeit, Sebastian; Bockamp, Ernesto; Mundlos, Stefan; Kornak, Uwe; Oheim, Ralf; Amling, Michael; Schinke, Thorsten; David, Jean-Pierre.

in: SCI TRANSL MED, Jahrgang 10, Nr. 466, 07.11.2018, S. eaau7137.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Luther, J, Yorgan, TA, Rolvien, T, Ulsamer, L, Koehne, T, Liao, N, Keller, D, Vollersen, N, Teufel, S, Neven, M, Peters, S, Schweizer, M, Trumpp, A, Rosigkeit, S, Bockamp, E, Mundlos, S, Kornak, U, Oheim, R, Amling, M, Schinke, T & David, J-P 2018, 'Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand', SCI TRANSL MED, Jg. 10, Nr. 466, S. eaau7137. https://doi.org/10.1126/scitranslmed.aau7137

APA

Luther, J., Yorgan, T. A., Rolvien, T., Ulsamer, L., Koehne, T., Liao, N., Keller, D., Vollersen, N., Teufel, S., Neven, M., Peters, S., Schweizer, M., Trumpp, A., Rosigkeit, S., Bockamp, E., Mundlos, S., Kornak, U., Oheim, R., Amling, M., ... David, J-P. (2018). Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand. SCI TRANSL MED, 10(466), eaau7137. https://doi.org/10.1126/scitranslmed.aau7137

Vancouver

Luther J, Yorgan TA, Rolvien T, Ulsamer L, Koehne T, Liao N et al. Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand. SCI TRANSL MED. 2018 Nov 7;10(466):eaau7137. https://doi.org/10.1126/scitranslmed.aau7137

Bibtex

@article{fd909040bc1342c895c956a09060730e,
title = "Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand",
abstract = "WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis.",
keywords = "Journal Article",
author = "Julia Luther and Yorgan, {Timur Alexander} and Tim Rolvien and Lorenz Ulsamer and Till Koehne and Nannan Liao and Daniela Keller and Nele Vollersen and Stefan Teufel and Mona Neven and Stephanie Peters and Michaela Schweizer and Andreas Trumpp and Sebastian Rosigkeit and Ernesto Bockamp and Stefan Mundlos and Uwe Kornak and Ralf Oheim and Michael Amling and Thorsten Schinke and Jean-Pierre David",
note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2018",
month = nov,
day = "7",
doi = "10.1126/scitranslmed.aau7137",
language = "English",
volume = "10",
pages = "eaau7137",
journal = "SCI TRANSL MED",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "466",

}

RIS

TY - JOUR

T1 - Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand

AU - Luther, Julia

AU - Yorgan, Timur Alexander

AU - Rolvien, Tim

AU - Ulsamer, Lorenz

AU - Koehne, Till

AU - Liao, Nannan

AU - Keller, Daniela

AU - Vollersen, Nele

AU - Teufel, Stefan

AU - Neven, Mona

AU - Peters, Stephanie

AU - Schweizer, Michaela

AU - Trumpp, Andreas

AU - Rosigkeit, Sebastian

AU - Bockamp, Ernesto

AU - Mundlos, Stefan

AU - Kornak, Uwe

AU - Oheim, Ralf

AU - Amling, Michael

AU - Schinke, Thorsten

AU - David, Jean-Pierre

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2018/11/7

Y1 - 2018/11/7

N2 - WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis.

AB - WNT1 mutations in humans are associated with a new form of osteogenesis imperfecta and with early-onset osteoporosis, suggesting a key role of WNT1 in bone mass regulation. However, the general mode of action and the therapeutic potential of Wnt1 in clinically relevant situations such as aging remain to be established. Here, we report the high prevalence of heterozygous WNT1 mutations in patients with early-onset osteoporosis. We show that inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures in mice. In contrast, conditional Wnt1 expression in osteoblasts promoted rapid bone mass increase in developing young, adult, and aged mice by rapidly increasing osteoblast numbers and function. Contrary to current mechanistic models, loss of Lrp5, the co-receptor thought to transmit extracellular WNT signals during bone mass regulation, did not reduce the bone-anabolic effect of Wnt1, providing direct evidence that Wnt1 function does not require the LRP5 co-receptor. The identification of Wnt1 as a regulator of bone formation and remodeling provides the basis for development of Wnt1-targeting drugs for the treatment of osteoporosis.

KW - Journal Article

U2 - 10.1126/scitranslmed.aau7137

DO - 10.1126/scitranslmed.aau7137

M3 - SCORING: Journal article

C2 - 30404864

VL - 10

SP - eaau7137

JO - SCI TRANSL MED

JF - SCI TRANSL MED

SN - 1946-6234

IS - 466

ER -