Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin

Standard

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.

In: J CELL BIOL, Vol. 200, No. 4, 18.02.2013, p. 537-49.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{4e607f92c2a645219cbb9986c1651824,
title = "Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin",
abstract = "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.",
keywords = "Animals, Bone Resorption, Cell Differentiation, Gene Expression Profiling, Mice, Mice, Inbred C57BL, Osteoclasts, Osteogenesis, Osteoprotegerin, Receptors, G-Protein-Coupled, Receptors, Wnt, Wnt Signaling Pathway, Wnt3A Protein, beta Catenin",
author = "Joachim Albers and Johannes Keller and Anke Baranowsky and Beil, {Frank Timo} and Philip Catala-Lehnen and Jochen Schulze and Michael Amling and Thorsten Schinke",
year = "2013",
month = feb,
day = "18",
doi = "10.1083/jcb.201207142",
language = "English",
volume = "200",
pages = "537--49",
journal = "J CELL BIOL",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin

AU - Albers, Joachim

AU - Keller, Johannes

AU - Baranowsky, Anke

AU - Beil, Frank Timo

AU - Catala-Lehnen, Philip

AU - Schulze, Jochen

AU - Amling, Michael

AU - Schinke, Thorsten

PY - 2013/2/18

Y1 - 2013/2/18

N2 - 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.

AB - 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.

KW - Animals

KW - Bone Resorption

KW - Cell Differentiation

KW - Gene Expression Profiling

KW - Mice

KW - Mice, Inbred C57BL

KW - Osteoclasts

KW - Osteogenesis

KW - Osteoprotegerin

KW - Receptors, G-Protein-Coupled

KW - Receptors, Wnt

KW - Wnt Signaling Pathway

KW - Wnt3A Protein

KW - beta Catenin

U2 - 10.1083/jcb.201207142

DO - 10.1083/jcb.201207142

M3 - SCORING: Journal article

C2 - 23401003

VL - 200

SP - 537

EP - 549

JO - J CELL BIOL

JF - J CELL BIOL

SN - 0021-9525

IS - 4

ER -