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首页> 外文会议>Conference on Skeletal Biology and Medicine >Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization
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Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization

机译：CBL-磷脂酰肌醇3激酶相互作用差异地调节巨噬细胞菌落刺激因子介导的破骨细胞存活和细胞骨骼重组

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The Cbl protein is a key player in macrophage colony-stimulating factor (M-CSF)-induced signaling. To examine the role of Cbl in M-CSF-mediated cellular events, we used Cbl~(YF/YF) knockin mice in which the regulatory tyrosine 737, which when phosphorylated binds to the p85 subunit of phosphatidylinositol 3 kinase (PI3K), is substituted to phenylalanine. In ex vivo cultures, M-CSF and receptor activator of nuclear factor-KB ligand-mediated differentiation of bone marrow precursors from Cbl~(YF/YF) mice generated increased number of osteoclasts; however, osteoclast numbers in Cbl~(YF/YF) cultures were unchanged with increasing doses of M-CSF. We found that Cbl~(YF/YF) osteoclasts have enhanced intrinsic ability to survive, and this response was further augmented upon exposure to M-CSF. Treatment of osteoclasts with M-CSF-induced actin reorganization and lamellipodia formation in wild-type osteoclasts; however, in Cbl~(YF/YF) osteoclasts lamellipodia formation was compromised. Collectively, these results indicate that abrogation of the Cbl-PI3K interaction, although not affecting M-CSF-induced proliferation and differentiation of precursors, is required for regulation of survival and actin cytoskeletal reorganization of mature osteoclasts.
机译：CBL蛋白是巨噬细胞菌落刺激因子（M-CSF）的关键球员 - 诱导的信号传导。为了检查CBL在M-CSF介导的细胞事件中的作用，我们使用CBL〜（YF / YF）基团，其中调节酪氨酸737，当磷酸化结合磷脂酰肌醇3激酶（PI3K）的P85亚基结合时，是取代苯丙氨酸。在离体培养物中，核因子-Kb配体介导的骨髓前体的M-CSF和受体激活物来自CBL〜（YF / YF）小鼠产生的骨细胞数量增加;然而，CBL〜（YF / YF）培养物中的骨壳数不变，随着M-CSF的增加而不变。我们发现CBL〜（YF / YF）破骨细胞增强了内在的存活能力，并且在暴露于M-CSF时进一步增强该响应。用M-CSF诱导的肌动蛋白重组和野生型破骨细胞中的抗肌肽重组的骨核苷酸切开骨质体的处理;然而，在CBL〜（YF / YF）骨粒细胞中，损伤了层状粒细胞。总的来说，这些结果表明，CBL-PI3K相互作用缺失，尽管不影响M-CSF诱导的前体的增殖和分化，所以用于调节成熟骨细胞的存活和肌动蛋白细胞骨骼重组。

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