Control of bone formation by the serpentine receptor Frizzled-9
نویسندگان
چکیده
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.
منابع مشابه
The Wnt Serpentine Receptor Frizzled-9 Regulates New Bone Formation in Fracture Healing
Wnt signaling is a key regulator of bone metabolism and fracture healing. The canonical Wnt/β-catenin pathway is regarded as the dominant mechanism, and targeting this pathway has emerged as a promising strategy for the treatment of osteoporosis and poorly healing fractures. In contrast, little is known about the role of non-canonical Wnt signaling in bone. Recently, it was demonstrated that th...
متن کاملRole of Frizzled receptor expression on patients’ survival with gastrointestinal cancers: A systematic review with meta-analysis
Background: Frizzled receptors (FZD) play a pivotal role in the initiation and progression of a wide array of cancers. Dysregulated expression of FZD receptors is correlated with higher metastasis and invasive potential, as well as short survival in many malignancies. In this meta-analysis, we aimed to verify the prognostic value of FZD receptor expression on patients’ survival with different t...
متن کاملDecreased level of the anti-inflammatory adipokines, secreted frizzled-related protein 5 and adiponectin, in high cholesterol diet-induced atherosclerotic rats
Introduction: The involvement of secreted frizzled-related protein5 (SFRP5) and adiponectin, two important adipokines produced by adipocytes, in cardiovascular diseases demand further assessment. Therefore, in this study the relation of the adipokines and atherosclerosis was evaluated in Rat. Materials and methods: For the study, thirty male Wistar rats were divided into 2 groups (each group c...
متن کاملTrimeric G Protein-Dependent Frizzled Signaling in Drosophila
Frizzled (Fz) proteins are serpentine receptors that transduce critical cellular signals during development. Serpentine receptors usually signal to downstream effectors through an associated trimeric G protein complex. However, clear evidence for the role of trimeric G protein complexes for the Fz family of receptors has hitherto been lacking. Here, we show roles for the Galpha(o) subunit (Go) ...
متن کاملAntagonizing Wnt and FGF Receptors an Enemy from within (the ER)
In this issue of Cell, Yamamoto et al. (2005) describe a novel molecule, Shisa, which functions in the endoplastic reticulum (ER) to prevent maturation of Frizzled (Fz) serpentine receptors and fibroblast growth factor receptor (FGFR). Shisa thus antagonizes Wnt and FGF signaling cell-autonomously, thereby promoting anterior patterning in Xenopus.
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 192 شماره
صفحات -
تاریخ انتشار 2011