Connective tissue growth factor (CTGF/CCN2) is a downstream mediator for TGF-beta1-induced extracellular matrix production in osteoblasts
AuthorsArnott, John A.
Rico, Mario C.
Odgren, Paul R.
Safadi, Fayez F.
Popoff, Steven N.
UMass Chan AffiliationsDepartment of Cell Biology
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAnimals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Connective Tissue Growth Factor; Cyclins; Extracellular Matrix; Extracellular Matrix Proteins; Gene Expression Regulation; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Osteoblasts; RNA, Small Interfering; Rats; Transforming Growth Factor beta1
Medicine and Health Sciences
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AbstractConnective tissue growth factor (CTGF/CCN2) is a cysteine-rich, extracellular matrix (ECM) protein that acts as an anabolic growth factor to regulate osteoblast differentiation and function. Recent studies have identified CTGF as a downstream effector of transforming growth factor-beta1 (TGF-beta1) for certain functions in specific cell types. In this study, we examined the role of CTGF as a downstream mediator of TGF-beta1-induced ECM production and cell growth in osteoblasts. Using primary cultures, we demonstrated that TGF-beta1 is a potent inducer of CTGF expression in osteoblasts, and that this induction occurred at all stages of osteoblast differentiation from the proliferative through mineralization stages. TGF-beta1 treatment of osteoblasts increased the expression and synthesis of the ECM components, collagen and fibronectin. When CTGF-specific siRNA was used to prevent TGF-beta1 induction of CTGF expression, it also inhibited collagen and fibronectin production, thereby demonstrating the requirement of CTGF for their up-regulation. To examine the effects of TGF-beta1 on osteoblast cell growth, cultures were treated with TGF-beta1 during the proliferative stage. Cell number was significantly reduced and the cells exhibited a decrease in G1 cyclin expression, consistent with TGF-beta1-induced cell-cycle arrest. Cultures transfected with CTGF siRNA prior to TGF-beta1 treatment showed an even greater reduction in cell number, suggesting that TGF-beta1-induced growth arrest is independent of CTGF in osteoblasts. Collectively, these data demonstrate for the first time that CTGF is an essential downstream mediator for TGF-beta1-induced ECM production in osteoblasts, but these two growth factors function independently regarding their opposing effects on osteoblast proliferation.
SourceJ Cell Physiol. 2007 Mar;210(3):843-52. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32837
Related ResourcesLink to Article in PubMed