CXCL12/CXCR4 signal axis plays an important role in mediating bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells.
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.
Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Chen
C
Liu
Yaguang
Y
Weng
Taixian
T
Yuan
Hong
H
Zhang
Huili
H
Bai
Baolin
B
Li
Dandan
D
Yang
Ruyi
R
Zhang
Fang
F
He
Shujuan
S
Yan
Xiaoqin
X
Zhan
Qiong
Q
Shi
D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D055427:Growth Differentiation Factor 2 / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D050659:Core Binding Factor Alpha 1 Subunit; C100596:DLX5 protein, human; D055427:Growth Differentiation Factor 2; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C493709:RUNX2 protein, human; D019718:Receptors, CXCR4; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; C092037:ZBTB16 protein, human; D000469:Alkaline Phosphatase
Bone Morphogenetic Protein 9; CXCL 12; CXCR4; Mesenchymal Stem Cells; Osteogenic Differentiation.