title: Control of bone formation by the serpentine receptor Frizzled-9.
abstract: Although Wnt signaling in osteoblasts is of critical importance for the regulation of bone remodeling, it is not yet known which specific Wnt receptors of the Frizzled family are functionally relevant in this process. In this paper, we show that Fzd9 is induced upon osteoblast differentiation and that Fzd9(-/-) mice display low bone mass caused by impaired bone formation. Our analysis of Fzd9(-/-) primary osteoblasts demonstrated defects in matrix mineralization in spite of normal expression of established differentiation markers. In contrast, we observed a reduced expression of chemokines and interferon-regulated genes in Fzd9(-/-) osteoblasts. We also identified the ubiquitin-like modifier Isg15 as one potential downstream mediator of Fzd9 in these cells. Importantly, our molecular analysis further revealed that canonical Wnt signaling is not impaired in the absence of Fzd9, thus explaining the absence of a bone resorption phenotype. Collectively, our results reveal a previously unknown function of Fzd9 in osteoblasts, a finding that may have therapeutic implications for bone loss disorders.
authors.affiliation: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Albers
authors.forename: Jochen
authors.initials: J
authors.lastname: Schulze
authors.forename: F Timo
authors.initials: FT
authors.lastname: Beil
authors.forename: Matthias
authors.initials: M
authors.lastname: Gebauer
authors.forename: Anke
authors.initials: A
authors.lastname: Baranowsky
authors.forename: Johannes
authors.initials: J
authors.lastname: Keller
authors.forename: Robert P
authors.initials: RP
authors.lastname: Marshall
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wintges
authors.forename: Felix W
authors.initials: FW
authors.lastname: Friedrich
authors.forename: Matthias
authors.initials: M
authors.lastname: Priemel
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Schilling
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Rueger
authors.forename: Kerstin
authors.initials: K
authors.lastname: Cornils
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.forename: Thomas
authors.initials: T
authors.lastname: Streichert
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
authors.forename: Karl L
authors.initials: KL
authors.lastname: Insogna
authors.forename: Barbara
authors.initials: B
authors.lastname: Pober
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D051157:Frizzled Receptors; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D051157:Frizzled Receptors; C403212:Fzd9 protein, mouse; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins