Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells
Language: 
English
Abstract: 

Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells.

Author(s): 
Luo, Qing
Kang, Quan
Si, Weike
Jiang, Wei
Park, Jong Kyung
Peng, Ying
Li, Xinmin
Luu, Hue H.
Luo, Jeffrey
Montag, Anthony G.
Haydon, Rex C.
He, Tong-Chuan
Item Type: 
Journal Article
Publication Title: 
The Journal of Biological Chemistry
Journal Abbreviation: 
J. Biol. Chem.
Publication Date: 
Dec 31, 2004
Publication Year: 
2004
Pages: 
55958-55968
Volume: 
279
Issue: 
53
ISSN: 
0021-9258
DOI: 
10.1074/jbc.M407810200
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 15496414

Turabian/Chicago Citation

Qing Luo, Quan Kang, Weike Si, Wei Jiang, Jong Kyung Park, Ying Peng, Xinmin Li, Hue H. Luu, Jeffrey Luo, Anthony G. Montag, Rex C. Haydon and Tong-Chuan He. Dec 31, 2004. "Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells." The Journal of Biological Chemistry 279: 53: 55958-55968. 10.1074/jbc.M407810200.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1074/jbc.M407810200 | issn = 0021-9258 | volume = 279 | pages = 55958-55968 | last = Luo | first = Qing | coauthors = Kang, Quan, Si, Weike, Jiang, Wei, Park, Jong Kyung, Peng, Ying, Li, Xinmin, Luu, Hue H., Luo, Jeffrey, Montag, Anthony G., Haydon, Rex C., He, Tong-Chuan | title = Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells | journal = The Journal of Biological Chemistry | date = Dec 31, 2004 | pmid = | pmc = }} </ref>