Apc bridges Wnt/beta-catenin and BMP signaling during osteoblast differentiation of 16483 cells

作者：Miclea Razvan L; van der Horst Geertje; Robanus Maandag Els C; Lowik Clemens W G M; Oostdijk Wilma; Wit Jan M; Karperien Marcel^*

来源：Experimental Cell Research, 2011, 317(10): 1411-1421.

DOI：10.1016/j.yexcr.2011.03.007

• Apc
• beta-Catenin
• Wnt
• Osteoblast
• Differentiation

The canonical Wnt signaling pathway influences the differentiation of mesenchymal cell lineages in a quantitative and qualitative fashion depending on the dose of beta-catenin signaling. Adenomatous polyposis coil (Apc) is the critical intracellular regulator of beta-catenin turnover. To better understand the molecular mechanisms underlying the role of Apc in regulating the differentiation capacity of skeletal progenitor cells, we have knocked down Apc in the murine mesenchymal stem cell-like K5483 cells by stable expression of Apc-specific small interfering RNA. In routine culture, KSFrt-Apc(si) cells displayed a mesenchymal-like spindle shape morphology, exhibited markedly decreased proliferation and increased apoptosis. Apc knockdown resulted in upregulation of the Wnt/beta-catenin and the BMP/Smad signaling pathways, but osteogenic differentiation was completely inhibited. This effect could be rescued by adding high concentrations of BMP-7 to the differentiation medium. Furthermore, KSFrt-Apc(si) cells showed no potential to differentiate into chondrocytes or adipocytes.
These results demonstrate that Apc is essential for the proliferation, survival and differentiation of KS483 cells. Apc knockdown blocks the osteogenic differentiation of skeletal progenitor cells, a process that can be overruled by high BMP signaling.

• 出版日期2011-6-10