Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin
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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, Jahrgang 200, Nr. 4, 18.02.2013, S. 537-49.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -