Although these catabolic factors were counteracted by even higher and increasing expression levels of their natural endogeneous inhibitors such as TIMP-1, TIMP-2, TIMP-3 and TIMP-4, we recoded declining levels of aggrecan and collagen II with increased severity of disc degeneration [31, 32, 34–36]. This evidence concerns the gene TIMP4 and intervertebral disk degenerative disorder.