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23 January 2019

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Int J Med Sci 2013; 10(9):1181-1192. doi:10.7150/ijms.6657

Research Paper

CXCL12/CXCR4 Signal Axis Plays an Important Role in Mediating Bone Morphogenetic Protein 9-induced Osteogenic Differentiation of Mesenchymal Stem Cells

Chen Liu1*, Yaguang Weng1*, Taixian Yuan1, Hong Zhang2, Huili Bai1, Baolin Li1, Dandan Yang1, Ruyi Zhang1, Fang He1, Shujuan Yan1, Xiaoqin Zhan1, Qiong Shi1,✉

1. Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China;
2. Department of Laboratory Medicine, Jinan Sixth Hospital, Zhangqiu250200, China.
* These authors contributed equally to this work.


Mesenchymal progenitor stem cells (MPCs) are a group of bone marrow stromal progenitor cells processing osteogenic, chondrogenic, adipogenic and myogenic lineages differentiations. Previous studies have demonstrated that bone morphogeneic protein 9(BMP9) is one of the most osteogenic BMPs both in vitro and in vivo, however, the underlying molecular mechanism of osteogenesis induced by BMP9 is needed to be deep explored. Here, we used the recombinant adenoviruses assay to introduce BMP9 into C3H10T1/2 mesenchymal stem cells to elucidate the role of CXCL12/CXCR4 signal axis during BMP9-incuced osteogenic differentiation. The results showed that CXCL12 and CXCR4 expressions were down-regulated at the stage of BMP9-induced osteogenic differentiation, in a dose- and time-dependent. Pretreatment of C3H10T1/2 cells with CXCL12/CXCR4 could significantly affect the early and mid osteogenic markers alkaline phosphatase (ALP), osteocalcin (OCN), the transcription factors of Runx2, Osx, Plzf and Dlx5 expression, through activating the Smad, MAPK signaling pathway. Addition of exogenous CXCL12 did not affect the changes of the late osteogenic marker calcium deposition. Thus, our findings suggest a co-requirement of the CXCL12/CXCR4 signal axis in BMP9-induced the early- and mid-process of osteogenic differentiation of MSCs.

Keywords: CXCL 12, CXCR4, Bone Morphogenetic Protein 9, Mesenchymal Stem Cells, Osteogenic Differentiation.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Liu C, Weng Y, Yuan T, Zhang H, Bai H, Li B, Yang D, Zhang R, He F, Yan S, Zhan X, Shi Q. CXCL12/CXCR4 Signal Axis Plays an Important Role in Mediating Bone Morphogenetic Protein 9-induced Osteogenic Differentiation of Mesenchymal Stem Cells. Int J Med Sci 2013; 10(9):1181-1192. doi:10.7150/ijms.6657. Available from