Disease relevance of MMP13

• The inhibitory activity was also confirmed by a decrease in MMP-13 release from human chondrosarcoma cell line SW1353 with an IC50 value of 17 nM [1].
• At hypertrophy, when mineral content was maximal, type II collagen was reduced maximally in content coincident with a peak of cleavage of this molecule by collagenase when matrix metalloproteinase 13 (MMP-13) expression was maximal [2].
• Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis [3].

High impact information on MMP13

• Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration [4].
• To assess the contribution of matrix metalloproteinase (MMP)-13 to NO-mediated EC migration, we used RNA interference to silence MMP-13 expression in ECs [4].
• In untreated cells MMP-13 was localized to caveolae, forming a complex with caveolin-1 [4].
• The cleavage product obtained after MMP-13 digestion was identical to that observed in cleaved fibromodulin from cartilage explant cultures stimulated with interleukin-1 [5].
• In solution, digestion of this substrate with matrix metalloproteinase (MMP)-2, -9, -8, and -13 demonstrated that only MMP-13 was capable to efficiently cleave it [5].

Biological context of MMP13

• A strong up-regulation of MMP13 expression was measured at day 12 in floating gels [6].
• Gene expression experiments by real-time RT-PCR showed that the expression of type II collagen and aggrecan was increased in the MMP-sensitive hydrogels, whereas the expression level of MMP-13 was increased in the MMP-insensitive hydrogels [7].
• The levels of cathepsin K, matrix metallo proteinase (MMP)-9, and MMP-13 mRNAs in the cells attached to dentine were also analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) [8].

Anatomical context of MMP13

• MMP-13 treatment of fresh articular cartilage also produced the fragment under study [5].
• Proteolysis involving matrix metalloproteinase 13 (collagenase-3) is required for chondrocyte differentiation that is associated with matrix mineralization [9].
• A nontoxic carboxylate inhibitor of MMP-13 prevents this differentiation; it suppresses expression of type X collagen, Cbfal, and MMP-13 and inhibits increased calcium incorporation in addition to inhibiting degradation of type II collagen in the extracellular matrix [9].
• Samples were collected at 0, 6, 12, 18, 24, and 48 h (corpora lutea) after GnRH injection (n = 5-6 per time point) and amounts of MMP-1 and MMP-13 mRNA and protein determined using dot blot or semiquantitative RT-PCR and Western blot analyses [10].

Associations of MMP13 with chemical compounds

• Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix metalloproteinase-13 [5].
• In human primary chondrocytes, the production of matrix metalloproteinase-13 and -1 (MMP-13 and -1) and prostaglandin E2 (PGE2) was induced by interleukin-1beta [1].
• Glucosamine was effective in suppressing IL-1-induced mRNA expression of MMP-13, Agg-1, and Agg-2, whereas CS was effective in decreasing IL-1-induced MMP-13 transcript at 24 hours [11].
• MMP-13 cleaved rbAgg within the IGD, but cleaved more rapidly at a site within the CS domains, suggesting a role in C-terminal processing of aggrecan [12].

Regulatory relationships of MMP13

• Cyclic hydrostatic pressure downregulated the expression of MMP-13 and type I collagen and upregulated expression of TIMP-1 compared to the unloaded controls [13].

Other interactions of MMP13

• RESULTS: Upregulated MMP-3, MMP-13, and Agg-1 transcripts at 24 hours were repressed by the GLN and CS combination by at least approximately 6-fold [11].
• Mammalian expression of full-length bovine aggrecan and link protein: formation of recombinant proteoglycan aggregates and analysis of proteolytic cleavage by ADAMTS-4 and MMP-13 [12].

Analytical, diagnostic and therapeutic context of MMP13

• Matrix metalloproteinase (MMP)-1, MMP-13, and tissue inhibitor of metalloproteinase 1 release were measured by specific enzyme linked immunosorbent assays (ELISAs), and collagenolytic activity was measured by a bioassay using radiolabelled collagen [14].

References