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

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.

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.

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.

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