FIGURE 8.

Increased aggrecan degradation is correlated with SDC4 and ADAMTS-5 protein levels in degenerate human NP tissues. A and B, Western blot analysis of ADAMTS generated aggrecan neoepitopes in human degenerate NP tissue samples using A, anti-ARGSVIL and B, anti-NITEGE antibodies. Both ARGSVIL and NITEGE neoepitope levels are significantly higher in all the degenerate NP samples compared with control tissue. Control sample showed undetectable levels of these aggrecan degradation products. Samples from three different patients were used for each degenerative grade. C, SDC4 and D, ADAMTS-5 expression levels in corresponding human degenerate NP samples. Degenerate samples that exhibit high level of aggrecan neoepitope accumulation also showed a high expression of both SDC4 and ADAMTS-5. Expression of SDC4 and ADAMTS-5 was very low in control sample. E, a proposed model of relationship between inflammatory cytokines (TNF-α, IL-1β), SDC4, and ADAMTS-5 in NP cells. During degeneration high levels of inflammatory cytokines TNF-α and IL-1β transcriptionally induce SDC4 expression through NF-κB signaling pathway. Increased level of SDC4 binds and anchors ADAMTS-5 on cell surface for processing and results in its activation. Active ADAMTS-5 cleaves aggrecan matrix resulting in loss of water binding capacity and disc height.