CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
Marrow mesenchymal stem cells are pluripotent progenitors that can differentiate into bone, cartilage, muscle, and fat cells. Wnt signaling has been implicated in regulating osteogenic differentiation of mesenchymal stem cells. Here, we analyzed the gene expression profile of mesenchymal stem cells that were stimulated with Wnt3A. Among the 220 genes whose expression was significantly changed by 2.5-fold, we found that three members of the CCN family, CCN1/Cyr61, CCN2/connective tissue growth factor (CTGF), and CCN5/WISP2, were among the most significantly up-regulated genes. We further investigated the role of CCN1/Cyr61 in Wnt3A-regulated osteogenic differentiation. We confirmed that CCN1/Cyr61 was up-regulated at the early stage of Wnt3A stimulation. Chromatin immunoprecipitation analysis indicates that CCN1/Cyr61 is a direct target of canonical Wnt/beta-catenin signaling. RNA interference-mediated knockdown of CCN1/Cyr61 expression diminished Wnt3A-induced osteogenic differentiation. Furthermore, exogenously expressed CCN1/Cyr61 was shown to effectively promote mesenchymal stem cell migration. These findings suggest that tightly regulated CCN1/Cyr61 expression may play an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
Molecular Oncology Laboratory, University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL 60637.
Weike
W
Si
Quan
Q
Kang
Hue H
HH
Luu
Jong Kyung
JK
Park
Qing
Q
Luo
Wen-Xin
WX
Song
Wei
W
Jiang
Xiaoji
X
Luo
Xinmin
X
Li
Hong
H
Yin
Anthony G
AG
Montag
Rex C
RC
Haydon
Tong-Chuan
TC
He
D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000032:analysis; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D047369:Chromatin Immunoprecipitation; D055515:Cysteine-Rich Protein 61; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D040081:Protein Array Analysis; D034622:RNA Interference; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D000469:Alkaline Phosphatase