Participation of intracellular cysteine proteinases, in particular cathepsin B, in degradation of collagen in periosteal tissue explants

Abstract

Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractThe involvement of cysteine proteinases in the degradation of soft connective tissue collagen was studied in cultured periosteal explants. Using cysteine proteinase inhibitors that were active intracellularly or extracellularly (Ep453 and Ep475, respectively), it was shown that over-all collagen degradation, as measured by the release of hydroxyproline, decreased significantly on inhibition of the intracellular pool of cysteine proteinases by Ep453. This inhibitor also induced an accumulation of intracellular fibrillar collagen in fibroblasts, indicating a decreased degradation of phagocytosed collagen. The extracellular inhibitor, Ep475, had minor or no effects.Histochemical analysis using a substrate for the cysteine proteinases cathepsins B and L revealed a high level of enzyme activity, which was completely blocked in explants preincubated with a selective intracellular inhibitor of cathepsin B, Ca074-Me. Moreover, the cathepsin B inhibitor strongly affected collagen degradation, decreasing the release of hydroxyproline and increasing the accumulation of phagocytosed collagen. These effects were comparable or slightly stronger than those found with the general intracellular inhibitor (Ep453). Taken together, these data strongly suggest that intracellular cysteine proteinases, in particular cathepsin B, play an important role in the digestion of soft connective tissue collagen.

The impact of glycosylation on HLA–DR1–restricted T cell recognition of type II collagen in a mouse model

“…Dense membrane fractions corresponding to lysosomes digested CII at low pH to generate fragments containing the glycosylated CII epitope that could be presented by prefixed APCs. Degradation of CII was blocked by inhibitors of serine and cysteine proteinases, which is consistent with previous studies implicating cysteine proteinases (cathepsins B, K, L, N, and S [41][42][43]) as well as serine proteinases (44) in intracellular CII degradation and antigen presentation (20). Inhibitors of serine proteinases, cysteine proteinases, aspartic proteinases, and metalloproteinases reduced the productive processing of the glycosylated epitope, and to a lesser extent, the nonglycosylated epitope, which again, is consistent with differential processing of CII for presentation of the glycosylated and nonglycosylated CII epitope.…”

Enhancement of gingival inflammation induced by synergism of IL-1^|^beta; and IL-6

“…7B, IL-6/sIL-6R induced significantly cathepsin B secretion in HGFs in agreement with our previous report (30). Cathepsin B degrades directly collagen fibers, and the protease contributes to collagen degradation indirectly through activation of MMP-1 (3,4). Therefore, these results encourage that MMP-1 and cathepsin B released from HGFs co-stimulated with both IL-1β and IL-6/sIL-6R might act cooperacient cell surface IL-6R to bind appreciable levels of IL-6 (19).…”

Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology

“…Compared to the biceps brachii tendon, the control supraspinatus showed increased levels of all MMP activities, particularly in older tendons with respect to MMP-1 activity, and especially with respect to gelatinase (MMP-2) activities. As described above, the gelatinase activity may account for the significantly lower amount of denatured collagen remaining in the tissue compared to the biceps brachii tendon, although other proteinases and phagocytic processes may also be involved in collagen turnover (Creemers et al, 1998).…”

“…There was also no direct association between levels of enzyme activity and the % D-Asp. This discrepancy may arise because other MMPs and proteinases (such as cathepsins) are potentially involved in tendon collagen turnover, and a proportion is also likely to be degraded by a phagocytic route (Creemers et al, 1998). However, it is clear that the measurement of enzyme activity at the time of tissue sampling does not necessarily reflect previous levels of enzyme activity and matrix turnover.…”