Ji Caixia, Liu Xiaohua, Xu Li, Yu Tingting, Dong Chaoqun, Luo Jinyong
Department of Laboratory Medicine, M.O.E. Key Laboratory of Laboratory Medicine Diagnostics, Chongqing Medical University, Chongqing 400016,China.
Int J Mol Sci. 2017 Jun 23;18(7):1348. doi: 10.3390/ijms18071348.
As one of the least studied bone morphogenetic proteins (BMPs), BMP9 is highly capable of promoting osteogenic differentiation. However, the underlying mechanism involved remains largely unknown. Recent studies have demonstrated that RUNX1 (runt-related transcription factor 1) is essential in osteoblast/chondrocyte maturation. In this study, we investigated the function of RUNX1 in BMP9-induced osteogenic of murine mesenchymal stem cell line (C3H10T1/2) and murine multi-lineage cell lines (C2C12 and MEFs). Our data showed that BMP9 promoted the endogenous expression of RUNX1 in C3H10T1/2, C2C12 and MEFs. Moreover, RUNX1 was probably a direct target of BMP9/Smad signaling. BMP9-induced osteogenic differentiation was enhanced by overexpression of RUNX1, whereas inhibited by knockdown RUNX1 in C3H10T1/2, C2C12 and MEFs. Further mechanism studies demonstrated that RUNX1 might affect BMP9-induced phosphorylation of Smad1/5/8, but not the phosphorylation of p38 and ERK1/2.Our results suggest that RUNX1 may be an essential modulator in BMP9- induced osteogenic differentiation of MSCs (Mesenchymal stem cells).
作为研究最少的骨形态发生蛋白（BMPs）之一，BMP9具有很强的促进成骨分化的能力。然而，其潜在机制仍 largely未知。最近的研究表明，RUNX1（ runt相关转录因子1）在成骨细胞/软骨细胞成熟过程中至关重要。在本研究中，我们研究了RUNX1在BMP9诱导的小鼠间充质干细胞系（C3H10T1/2）和小鼠多谱系细胞系（C2C12和MEFs）成骨过程中的功能。我们的数据表明，BMP9促进了C3H10T1/2、C2C12和MEFs中RUNX1的内源性表达。此外，RUNX1可能是BMP9/Smad信号的直接靶点。在C3H10T1/2、C2C12和MEFs中，RUNX1的过表达增强了BMP9诱导的成骨分化，而RUNX1的敲低则抑制了这种分化。进一步的机制研究表明，RUNX1可能影响BMP9诱导的Smad1/5/8磷酸化，但不影响p38和ERK1/2的磷酸化。我们的结果表明，RUNX1可能是BMP9诱导间充质干细胞（MSCs）成骨分化的关键调节因子。
