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. Author manuscript; available in PMC: 2017 May 1.
Published in final edited form as: Matrix Biol. 2016 Jan 18;52-54:355–362. doi: 10.1016/j.matbio.2016.01.005

Figure 3. The role of SDC4 in the degenerating nucleus pulposus.

Figure 3

In the degenerating NP, the increase in inflammatory cytokines TNF-α and IL-1β drives the expression of catabolic enzymes MMP-3 and ADAMTS-5, and have also been shown to regulate SDC4 expression via MAPK and NF-κB signalling pathways. SDC4 selectively interacts with ADAMTS-5 at the cell surface promoting its activation and subsequent cleavage of aggrecan. SDC4 is also important in controlling TNF-dependent MMP-3 expression via MAPK and NF-κB pathways. The expression of these catabolic factors leads to the degeneration of the IVD. Likewise, IL-1β induced SDC4 is supressed by CCN2/CTGF bound to integrins αvβ3 and α5β1. Additionally, anabolic growth factor TGFβ inhibits NF-κB signalling in NP cells, supressing SDC4 and MMP-3 expression.