Studies by Alsalameh and colleagues [24] on synovial fibroblasts from rheumatoid arthritis patients and osteoarthritis patients have indicated that there is a differential expression of the two TNF receptors in these cells and that, while both receptors can mediate the effect of TNF-α on TIMP1 expression, PGE2 (prostaglandin E2) IL-6 and MMP-1 regulations are mediated exclusively via TNF-R1, suggesting that, although the expression of TNF-R1 does not change with degeneration in the IVD, signalling through this receptor is critical for upregulation of degradative processes. This evidence concerns the gene TNFRSF1A and rheumatoid arthritis.