Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Horm Metab Res. 2011 Mar;43(3):183-7. doi: 10.1055/s-0030-1270527. Epub 2011 Jan 24.
Menin promotes the commitment of pluripotent mesenchymal stem cells to the osteoblast lineage by interacting with the BMP-2 signaling molecules Smad1/5, and Runx2. However, the relationship between menin and the Wnt-β-catenin pathway in bone is unclear. Reduction of menin expression by transfection of a menin antisense construct did not alter the levels of β-catenin in mouse mesenchymal C2C12 and osteoblastic MC3T3-E1 cells. However, menin co-immunoprecipitated with β-catenin as well as LEF-1 in C2C12 and MC3T3-E1 cells. Reduction of menin expression by antisense menin transfection antagonized β-catenin-induced transcriptional activity of the pGL3-OT luciferase reporter construct in C2C12 and MC3T3-E1 cells. Antisense menin transfection antagonized the BMP-2 and β-catenin-stimulated increases in Runx2 and alkaline phosphatase levels in C2C12 cells. The data show that menin interacts with β-catenin in mouse mesenchymal and osteoblastic cells, and suggest that the interaction is important for osteoblast differentiation.
Menin 通过与 BMP-2 信号分子 Smad1/5 和 Runx2 相互作用，促进多能间充质干细胞向成骨细胞谱系的分化。然而，menin 与骨中 Wnt-β-catenin 通路的关系尚不清楚。用 menin 反义构建体转染降低 menin 表达水平不会改变小鼠间充质 C2C12 和成骨细胞 MC3T3-E1 细胞中的 β-catenin 水平。然而，menin 与 C2C12 和 MC3T3-E1 细胞中的 β-catenin 以及 LEF-1 共免疫沉淀。用反义 menin 转染降低 menin 表达水平拮抗了 C2C12 和 MC3T3-E1 细胞中 pGL3-OT 荧光素酶报告基因构建体的 β-catenin 诱导的转录活性。反义 menin 转染拮抗了 BMP-2 和 β-catenin 刺激的 C2C12 细胞中 Runx2 和碱性磷酸酶水平的增加。这些数据表明，menin 在小鼠间充质和成骨细胞中与 β-catenin 相互作用，并表明这种相互作用对于成骨细胞分化很重要。
