Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration

While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration.Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.Proteins of the matrix metalloproteinase (MMP) family play an essential role in tissue homeostasis by initiating breakdown and reorganization of the extracellular matrix. While being tightly regulated in normal physiological processes (e.g. via tissue inhibitors of metalloproteases TIMPs), dysregulation of MMPs has been implicated in many diseases. During intervertebral disc (IVD) degeneration, the expression and activity of a number of MMPs is increased, including MMPs 1, 3, 7, 9 and 13 [1]. Proinflammatory cytokines such as IL-1β and TNF-α as well as bacterial endotoxins (e.g. lipopolysaccharide LPS) can stimulate expression of various MMPs (e.g. MMPs 1, 3, 9 and 13) in the IVD, as well as in cartilage [2-10].During the recent past, five new members in the MMP family have been identified: MMP24 to MMP28. MMP28, also known as epilysin and most closely related to MMP19, is a soluble MMP that contains an activation sequence recognized by the furin endoprotease following the pro-domain [11]. It is a well-conserved MMP, with great similarity (97%) in the catalytic domain between human and mouse and overall 85% identical amino acids [12]. MMP28 is strongly expressed in testis, as well as in bone, kidneys, lung, heart, colon, intestines, brain, skin and carcinomas [12-17]. It is also expressed in cartilage, synovium