Of particular note are the putative enzymes, some likely to be involved in matrix cross-linking (two yellow family members previously implicated in eggshell integrity, a heme peroxidase, and a small-molecule oxidoreductase) and others possibly involved in matrix proteolysis or adhesion (proteins related to cathepsins B and D).
However, the MMPs may be involved in matrix remodeling once the osteoclasts are finished.
The first evidence that IL-1 might be involved in matrix degredation in DIVD came in 1988 from in vitro experiments employing rabbit AF cells [ 40].
Recently, it was suggested that Pex11pγ may be involved in matrix protein import in Pex11pβ-deficient human fibroblasts (Ebberink et al., 2012).
Additionally, such strategies would probably require combined treatments to restrain the degenerative processes – such as inhibition of IL-1, which is significantly increased in IVD degeneration and has been shown to be involved in matrix degradation [ 18, 31].
Most of the S. cerevisiae PEX genes identified by the above approaches appear to be involved in matrix protein import namely PEX1, -2, -4, -5, -6, -7, -8, -10, -12, -13, -14, -15, -17, -18, -21, -22 (Table 2)—whereas two genes, PEX3 and PEX19, are proposed to be essential for the formation of functional peroxisomal membranes.
TMPRSS6 is a type II membrane-anchored serine protease that is involved in matrix remodeling processes in the liver [17], and is essential for normal iron homeostasis [18].
TIMP2 is involved in matrix degradation and invasion, and is down-regulated in Motif 1 cell lines in this study, which is consistent with its role in inhibiting matrix metalloproteinases, and agrees with the inverse correlation shown between S100A4 and TIMP2 in osteosarcoma cells [31].
Most elevated pathways found in the CD24+ are involved in matrix formation and remodeling.
CD44 is involved in matrix adhesion, lymphocyte activation, and the regulation of tumor proliferation.
The CD40-CD40L signaling pathway also is involved in matrix metalloproteinases (MMPs) expression, including MMP-9 [ 19, 20].
