β-Catenin levels influence rapid mechanical responses in osteoblasts

作者: Natasha Case , Meiyun Ma , Buer Sen , Zhihui Xie , Ted S. Gross

DOI: 10.1074/JBC.M801907200

关键词: GSK-3LRP5Beta-cateninCell biologyProtein kinase BBone cellWnt signaling pathwaySignal transductionBiologyCatenin

摘要: Mechanical loading of bone initiates an anabolic, anticatabolic pattern response, yet the molecular events involved in mechanical signal transduction are not well understood. Wnt/β-catenin signaling has been recognized promoting anabolism, and application strain shown to induce β-catenin activation. In this work, we have used a preosteoblastic cell line study effects dynamic on signaling. We found that caused rapid, transient accumulation active cytoplasm its translocation nucleus. This was followed by up-regulation target genes Wisp1 Cox2, with peak responses at 4 1 h strain, respectively. The increase temporally related activation Akt subsequent inactivation GSK3β, caveolin-1 required for these events. Application Dkk-1, which disrupts canonical Wnt/LRP5 signaling, did block strain-induced nuclear or Cox2 expression. Conditions increased basal levels, such as lithium chloride treatment repression expression, were enhance strain. summary, activates inactivates GSK3β allow translocation, Wnt through LRP5 is strain-mediated responses. Thus, serves both modulator effector signals cells.

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