Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo

In bone regeneration, there are some important cellular biological processes, such as mineralization, cell organization, and differentiation. In particular, vascularization into regenerative tissues is a key step for the survival of cells and tissues. In this study, to fabricate biomimetic-engineered bone, including vascular networks, we focused on connective tissue growth factor (CTGF), a multifunctional protein which could regulate the extracellular matrix remodeling. By combination with CTGF and hydroxyapatite (HAp) ceramics (2D) or apatite-fiber scaffold (AFS, 3D), we have fabricated bioactive materials. The CTGF-loaded HAp ceramics could enhance the cellular attachment through interaction with integrin and promote actin cytoskeletal reorganization. CTGF-loaded HAp also enhanced the differentiation of osteoblasts by integrin-mediated activation of the signaling pathway. Under co-culture conditions, both osteoblasts and endothelial cells in the CTGF-loaded AFS were stimulated by CTGF, and each cell could penetrate the central region of the scaffold in vitro and in vivo. Direct cell-cell interaction would also improve the functionality of cells in bone formation. These results suggest that coupling between effective optimized scaffold and CTGF with multifunction could provide better mimicking natural bone by stimulation of angiogenesis.

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Connective tissue growth factor causes EMT-like cell fate changes in vivo and in vitro

Journal of Cell Science ◽

10.1242/jcs.111302 ◽

2013 ◽

Vol 126 (10) ◽

pp. 2164-2175 ◽

Cited By ~ 48

Author(s):

S. Sonnylal ◽

S. Xu ◽

H. Jones ◽

A. Tam ◽

V. R. Sreeram ◽

...

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Cell Fate ◽

Connective Tissue Growth Factor ◽

Tissue Growth

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Connective tissue growth factor/CCN-2 is upregulated in epididymal and subcutaneous fat depots in a dietary-induced obesity model

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00654.2012 ◽

2013 ◽

Vol 304 (12) ◽

pp. E1291-E1302 ◽

Cited By ~ 16

Author(s):

Joanne T. M. Tan ◽

Susan V. McLennan ◽

Paul F. Williams ◽

Alireza Rezaeizadeh ◽

Lisa W.-Y. Lo ◽

...

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Adipocyte Differentiation ◽

Subcutaneous Fat ◽

Tissue Growth ◽

Mrna Levels ◽

Fat Depots

Connective tissue growth factor (CTGF), also known as CCN-2, is a cysteine-rich secreted protein that is involved in a range of biological processes, including regulation of cell growth and differentiation. Our previous in vitro studies have shown that CCN-2 inhibits adipocyte differentiation, although whether CCN-2 is regulated in vivo in adipogenesis is undetermined and was investigated in this study. C57BL/6 male mice were fed either standard laboratory chow (ND) or a diet high in fat (HFD; 45% fat) for 15 or 24 wk. HFD animals that gained >5 g in weight (termed HFD-fat) were insulin resistant and were compared with HFD-fed animals, which failed to gain weight (termed HFD-lean). HFD-fat mice had significantly increased CCN-2 mRNA levels in both the subcutaneous and epididymal fat pads, whereas CCN-2 mRNA was not induced in the epididymal site in HFD-lean mice. Also in HFD-fed animals, epididymal CCN-2 mRNA correlated positively with key genes involved in adipocyte differentiation, adiponectin and PPARγ ( P < 0.001 and P < 0.002, respectively). Additionally, epididymal CCN-2 mRNA correlated positively with two markers of tissue turnover, PAI-1 in HFD-fat mice only and TIMP-1, but only in the HFD-lean mice. Collectively, these findings suggest that CCN-2 plays a role in adipocyte differentiation in vivo and thus in the pathogenesis of obesity linked with insulin resistance.

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