Disease relevance of MMP20

• Expression of collagen XVIII and MMP-20 in developing teeth and odontogenic tumors [1].
• The full-length human enamelysin cDNA has been expressed in Escherichia coli, and the purified and refolded recombinant protein is able to degrade synthetic peptides used as substrates of MMPs, confirming that human enamelysin belongs to this family of proteases [2].
• No intracellular staining for enamelysin was detected in ameloblastomas or the ameloblastic portion of ameloblastic fibro-odontomas [3].
• Furthermore, enamelysin was also detected in globular amyloid masses and calcified foci in calcifying epithelial odontogenic tumors, hyaline droplets, small and large mineralized areas in adenomatoid odontogenic tumors, and a portion of ghost cells in calcifying odontogenic cysts [3].

High impact information on MMP20

• MMP-2 and MMP-20 were purified from over 150 g of porcine dentin powder and incubated with DSP-DGP and DPP [4].
• In healthy tissues, MMP-20 is observed in the enamel organ and pulp organ of developing teeth and is present only as an activated enzyme [5].
• Since type V collagen is not present in dental enamel but is an otherwise widely distributed collagen, and since only active MMP-20 has been observed in teeth, our data suggest that control of MMP-20 activity is primarily regulated by transcriptional means [5].
• We asked if the highly restricted MMP-20 expression pattern was associated with a broad substrate specificity that might preclude its expression in other tissues [5].
• Among the non-tooth tissues assayed, MMP-20 transcripts were identified only in minute quantities within the large intestine [5].

Biological context of MMP20

• MMP20 active-site mutation in hypomaturation amelogenesis imperfecta [6].
• Zymogram analysis demonstrated that this missense mutation abolished MMP20 proteolytic activity [6].
• No MMP20 mutations were found in the remaining 14 probands, underscoring the genetic heterogeneity of hypomaturation AI [6].
• The open reading frame of the cloned cDNA codes for a polypeptide of 483 amino acids and is extensively similar to the sequence of recently described porcine enamelysin, suggesting that the isolated cDNA codes for the human homologue of this enzyme [2].
• Finally, we have found that the human enamelysin gene (MMP-20) maps to chromosome 11q22, clustered to at least seven other members of the MMP gene family [2].

Anatomical context of MMP20

• Whereas MMP-19 mRNA is found widely expressed in body tissues, including the synovium of normal and rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel organ [7].
• Collagen XVIII is a basement membrane (BM) component, whereas MMP-20 (enamelysin) is a matrix metalloproteinase predominantly expressed in teeth [1].
• A brief review of dental enamel formation is presented, followed by a more detailed analysis of enamelysin and KLK4 expression, structure, and function [8].
• These in vitro results suggest that fluoride can alter the expression of MMP-20 by ameloblasts, resulting in a disturbance of the balance between MMP-20 and its substrate that may contribute to the retention of amelogenins in the formation of fluorosed enamel [9].
• Enamelysin is a tooth-specific protease that was initially isolated from porcine enamel organ and subsequently from human odontoblasts [3].

Associations of MMP20 with chemical compounds

• Cultured human fetus tooth organ ameloblast-lineage cells were exposed to 10 microM fluoride and analyzed for synthesis of MMP-20 [9].
• Two proteases have recently been cloned: EMSP-1 (enamel matrix serine protease-1), a serine protease, and enamelysin, a metalloprotease [10].
• MMP-20 releases the tyrosine rich amelogenin peptide (TRAP) from amelogenin [11].

Enzymatic interactions of MMP20

• Furthermore, recombinant porcine enamelysin was demonstrated to cleave recombinant porcine amelogenin at virtually all of the sites that have previously been described in vivo [12].
• Enamelysin cleaved the 32-kDa enamelin only after it was deglycosylated [13].
• We tested the hypothesis that MMP-20 is the protease that cleaves AMBN [14].

Other interactions of MMP20

• To determine the frequency of mutations in these genes, we analyzed 15 Turkish probands with autosomal-recessive hypomaturation AI for MMP20 and KLK4 gene mutations [6].
• Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently discovered members of the MMP family [7].
• Enamelysin (MMP-20) is the foremost enamel matrix-processing enzyme [8].
• Human enamelysin (MMP-20) has a domain organization similar to other MMPs, including a signal peptide, a prodomain with the conserved motif PRCGVPD involved in maintaining enzyme latency, a catalytic domain with a Zn-binding site, and a COOH-terminal fragment similar to the sequence of hemopexin [2].
• How do enamelysin and kallikrein 4 process the 32-kDa enamelin [13]?

Analytical, diagnostic and therapeutic context of MMP20

• Real-time polymerase chain reaction (PCR) showed that 10 microM NaF down-regulated MMP-20 mRNA expression to 28% of the levels found in the non-treated cells [9].
• Immunoblotting showed that 10 microM NaF down-regulated the synthesis of MMP-20 by 21% compared with control cells, but did not alter the amount of amelogenin or kalikrein-4 (KLK-4) synthesized by the cells [9].
• One-step sandwich enzyme immunoassay using monoclonal antibodies for detection of human enamelysin (MMP-20) [15].

References