MMP20 Cleaves E-Cadherin and Influences Ameloblast Development

Abstract

Dental enamel development occurs in stages as observed by the changing morphology of the ameloblasts that are responsible for enamel formation. During the secretory stage of development, proteins including MMP20 are secreted into the enamel matrix. MMP20 is required for proper enamel formation as mutation of the Mmp20 gene causes autosomal recessive amelogenesis imperfecta. Here, we examined in detail the morphology of the Mmp20-null ameloblast cell layer. Intriguingly, we found that the Mmp20-null mouse secretory stage ameloblasts retract their Tomes’ processes as if preparing to enter the maturation stage but later reextend their Tomes’ processes as if resuming the secretory stage. We also demonstrated that MMP20 cleaves epithelial cadherin, i.e. E-cadherin. Cadherins are transmembrane proteins with extracellular domains that provide adhesive contacts between neighboring cells. Their intracellular domains bind to the cell cytoskeleton through catenins, including β-catenin. When specific MMPs cleave the cadherin extracellular domain, β-catenin is released and may locate to the cell nucleus as a transcription factor. Therefore, MMP20 may influence ameloblast developmental progression through hydrolysis of cadherin extracellular domains with associated release of transcription factor(s).

Expression and roles of syndecan-4 in dental epithelial cell differentiation

“…RUNX2 is a key regulatory transcription factor that suppresses genes that are expressed during the secretory stage, such as AMGN and ENAM, and thus regulates enamel formation (28). MMP20 and KLK4 are proteases that break down enamel proteins to form a mineralized layer of enamel (23). Among the genes investigated in this study, they were the most profoundly affected genes when SDC4 expression was inhibited.…”

“…In this study, the anti-SDC4 antibody was the synthetic peptide surrounding the intracellular domain of SDC4 (22). Due to the fact that the cytoplasmic domains of the core protein are conserved, and the extracellular domain of SDC4 can be proteolytically cleaved, a process mediated by a variety of proteases of the MMP family, it can thus be suggested that the SDC4 ectodomain may be cleaved to the ameloblasts that synthesize MMP20 at the secretory stage (23).…”

Molar Incisor Hypomineralization: Morphological, Aetiological, Epidemiological and Clinical Considerations

“…Enamelysin (Mmp20), a matrix metalloproteinase, and the enamel serine protease kallikrein 4 (Klk4) are two major molecules involved in this process. (Wright et al, 2009, Bartlett et al, 2011 Mmp20 is expressed in secretory stage ameloblasts and also has effects on them maturation stage as well as on the mineralisation of mantle dentine. Klk4, present in both ameloblasts and odontoblasts, is expressed at the enamel transition and maturation phase.…”

“…In the maturation phase Runx2 induces Klk4 and upregulates basal membrane protein expression to induce ameloblast attachment to the enamel matrix. (Brook, 2009, Wrightet al, 2009, Bartlett et al, 2011 In general, systemic factors that disturb the ameloblasts during the secretory stage cause restrictions of crystal elongation and result in pathologically thin, or hypoplastic enamel. On the other hand, disturbances during the transitional and/or maturation stage of amelogenesis result in pathologically soft (hypomaturated, hypomineralised) enamel of normal thicknesses.…”

MMP20 and KLK4 activation and inactivation interactions in vitro

“…In addition to the role of processing enamel proteins, junctional complexes present on ameloblasts may also be cleaved by MMP20 to foster cell movement, which is necessary for the formation of the decussating enamel rod pattern. 10,11 Another proposed function of MMP20 is to activate KLK4. 12 …”