The interaction between CTGF and VEGF-A in the progression of intervertebral disc fibrosis.

Abstract

Background: Fibrosis in the extracellular matrix of nucleus pulposus (NP) is associated with intervertebral disc degeneration (IVDD). Both connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-A are responsible for the pathological basis of NP fibrosis. Our study aims to verify the interaction between CTGF and VEGF-A in a vitro NP cell model.

Methodology: Collected human NP tissues of different degeneration degree and isolated the NP cells from the non-degenerated NP tissues. Analysed the CTGF and VEGF-A gene expression in the naturally degenerated NP and IL-1β-induced degenerated NP cells. Additionally, interfered wit the CTGF and VEGF-A expression by exogenic protein treatment, siRNA transfection, or specific inhibitor. The expression of CTGF, VEGF-A, collagen I/II/III and aggrecan with protein or mRNA level was determined by immunological staining, western blotting and RT-PCR.

Results: CTGF and VEGF-A highly expressed in the late-term of degeneration compared to the middle-term, and their expressions were synergistic. Upregulating one of CTGF and VEGF-A could induce the overexpression of the other one and collagen I/III, but suppressed collagen II and aggrecan expression; Besides, the suppression of one of them could inhibited another and collagen I/III expression.

Conclusions: CTGF and VEGF-A increase in late IVDD. Prevent NP fibrosis by suppressing their interaction.