AMP-activated protein kinase attenuates Wnt/beta-catenin signaling in human osteoblastic Saos-2 cells

作者：Takatani Tomozumi^*; Minagawa Masanori; Takatani Rieko; Kinoshita Kaori; Kohno Yoichi

来源：Molecular and Cellular Endocrinology, 2011, 339(1-2): 114-119.

DOI：10.1016/j.mce.2011.04.003

• AMPK
• Metformin
• Wnt
• beta-Catenin
• Osteoblast

AMP-activated protein kinase (AMPK) is a key sensor of cellular energetic conditions. Recent studies suggest that AMPK affects osteoblast differentiation, although its role and mechanism are not fully understood. One of the most important signals in osteoblast differentiation is the Wnt/beta-catenin pathway which induces T-cell transcription factor 1 (TCF)-dependent transcription. Using human osteoblast-like Saos-2 cells, we determined whether AMPK modulates Wnt/beta-catenin signaling in osteoblasts. Chemical activators of AMPK (AICAR 15-aminoimidazole-4-carboxamide riboside], metformin) suppressed Wnt3a-induced TCF-dependent transcriptional activity. Transactivation by Wnt was potentiated by inhibiting beta-catenin degradation with lithium chloride (LiCl). LiCl-induced Wnt transactivation was suppressed by addition of metformin. Metformin increased the phosphorylation of beta-catenin and decreased beta-catenin protein levels leading to suppression of Wnt/beta-catenin signaling. Our present study showed that AMPK attenuates Wnt/beta-catenin signaling by reducing beta-catenin protein levels in osteoblast-like cells.

• 出版日期2011-6-6