Mesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts and chondrocytes. In vitro osteogenic differentiation is critical but the molecular mechanism has yet to be further clarified. The role of TGF-β activated kinase 1 (TAK1) in MSCs osteogenesis differentiation has not been reported. By adding si-TAK1 and rhTAK1, the osteogenic differentiation of MSCs was measured. Expression levels of the osteoblastic marker genes during osteogenic differentiation of MSCs were checked. As well as molecules involved in BMP and Wnt/β-catenin signaling pathways. The phosphorylation of p38 and JNK was also checked. TAK1 is essential for mineralization of MSCs at low concentration, but excessive rhTAK1 inhibits mineralization of MSCs. It up regulates the expression levels of bone sialoprotein (BSP), osteocalcin (OSC), Alkaline phosphatase (ALP), and RUNX2 during osteogenic differentiation of MSCs. It can also promote TGF-β/BMP-2 gene expression and β-catenin expression, and down regulate GSK-3β expression. Meanwhile, TAK1 promotes the phosphorylation of p38 and JNK. Additionally, TAK1 up regulates the expression of BMP-2 at all concentration under the inhibition of p38 and JNK. Our results suggested that TAK1 is essential in MSCs osteogenesis differentiation, and functions as a double-edged sword, probably through regulation of β-catenin and p38/JNK.

间充质干细胞（MSC）具有分化为成骨细胞和软骨细胞的能力。体外成骨细胞分化是至关重要的，但分子机制尚待进一步阐明。TGF-β激活激酶1（TAK1）在MSCs成骨分化中的作用尚未见报道。通过添加si-TAK1和rhTAK1，测量了MSC的成骨分化。检查成骨细胞分化过程中成骨细胞标记基因的表达水平。以及参与BMP和Wnt /β-catenin信号通路的分子。还检查了p38和JNK的磷酸化。TAK1对于低浓度的MSC矿化至关重要，但是过量的rhTAK1会抑制MSC的矿化。它在MSCs成骨分化过程中上调骨唾液蛋白（BSP），骨钙蛋白（OSC），碱性磷酸酶（ALP）和RUNX2的表达水平。它还可以促进TGF-β/ BMP-2基因表达和β-catenin表达，并下调GSK-3β表达。同时，TAK1促进p38和JNK的磷酸化。此外，TAK1在p38和JNK的抑制下在所有浓度上调BMP-2的表达。我们的研究结果表明，TAK1在MSC的成骨分化中必不可少，并可能通过调节β-catenin和p38 / JNK发挥双刃剑的作用。