scholarly journals Functions of KLK4 and MMP-20 in dental enamel formation

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Yuhe Lu ◽  
Petros Papagerakis ◽  
Yasuo Yamakoshi ◽  
Jan C.-C. Hu ◽  
John D. Bartlett ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Dental Enamel ◽  
Organic Matrix ◽  
Maturation Stage ◽  
Protein Cleavage ◽  
Enamel Formation ◽  
Residual Protein ◽  
Kallikrein 4 ◽  
Enamel Protein ◽  
Enamel Proteins

Abstract Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin (MMP-20). The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory-stage ameloblasts. Enamel protein-cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. KLK4 is secreted by transition- and maturation-stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

scholarly journals The genetics of amelogenesis imperfecta: a review of the literature

2005 ◽  
Vol 13 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Maria Cristina Leme Godoy dos Santos ◽  
Sergio Roberto Peres Line
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Dental Enamel ◽  
Matrix Proteins ◽  
Specific Gene ◽  
Enamel Formation ◽  
Complex Process ◽  
Different Types ◽  
Kallikrein 4

A melogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Enamel findings in AI are highly variable, ranging from deficient enamel formation to defects in the mineral and protein content. Enamel formation requires the expression of multiple genes that transcribes matrix proteins and proteinases needed to control the complex process of crystal growth and mineralization. The AI phenotypes depend on the specific gene involved, the location and type of mutation, and the corresponding putative change at the protein level. Different inheritance patterns such as X-linked, autosomal dominant and autosomal recessive types have been reported. Mutations in the amelogenin, enamelin, and kallikrein-4 genes have been demonstrated to result in different types of AI and a number of other genes critical to enamel formation have been identified and proposed as candidates for AI. The aim of this article was to present an evaluation of the literature regarding role of proteins and proteinases important to enamel formation and mutation associated with AI.

Genes and Related Proteins Involved in Amelogenesis Imperfecta

2005 ◽  
Vol 84 (12) ◽  
pp. 1117-1126 ◽  
Author(s):  
G. Stephanopoulos ◽  
M.-E. Garefalaki ◽  
K. Lyroudia
Keyword(s):  
Candidate Genes ◽  
Current Knowledge ◽  
Dental Enamel ◽  
Amelogenesis Imperfecta ◽  
Enamel Formation ◽  
Biomineralization Process ◽  
Genes Encoding ◽  
Kallikrein 4 ◽  
Enamel Proteins ◽  
Related Proteins

Dental enamel formation is a remarkable example of a biomineralization process. The exact mechanisms involved in this process remain partly obscure. Some of the genes encoding specific enamel proteins have been indicated as candidate genes for amelogenesis imperfecta. Mutational analyses within studied families have supported this hypothesis. Mutations in the amelogenin gene ( AMELX) cause X-linked amelogenesis imperfecta, while mutations in the enamelin gene ( ENAM) cause autosomal-inherited forms of amelogenesis imperfecta. Recent reports involve kallikrein-4 ( KLK4), MMP-20, and DLX3 genes in the etiologies of some cases. This paper focuses mainly on the candidate genes involved in amelogenesis imperfecta and the proteins derived from them, and reviews current knowledge on their structure, localization within the tissue, and correlation with the various types of this disorder.

Enamel Proteases in Secretory and Maturation Enamel of Rats Ingesting 0 and 100 ppm Fluoride in Drinking Water

1989 ◽  
Vol 3 (2) ◽  
pp. 199-202 ◽  
Author(s):  
P.K. Denbesten ◽  
L.M. Heffernan
Keyword(s):  
Drinking Water ◽  
Proteolytic Activity ◽  
Dental Enamel ◽  
Organic Content ◽  
Maturation Stage ◽  
Enamel Formation ◽  
Early Maturation ◽  
Coomassie Blue ◽  
Enamel Proteins ◽  
And Control

Dental enamel formed during ingestion of high levels of fluoride in drinking water has an increased organic content in the maturation stage, which may be due to a delay in the breakdown of amelogenins during the early-maturation stage of enamel formation. This delay in the breakdown of amelogenins in fluorosed enamel suggests an effect of fluoride on enamel proteases which hydrolyze the early secreted enamel proteins. In this study, we compared the proteases present in fluorosed and control secretory-stage and maturation-stage enamel. Enamel was demineralized and separated in SDS gels containing 0.1% gelatin. After incubation in 100 mmol/L Tris-HCI, pH 8, with 10 mmol/L CaCl2, the gels were stained with Coomassie Blue, and proteases were seen as clear zones of degraded gelatin. Similar bands of proteolytic activity were seen in fluorosed and in control enamel. In the maturation stage, more proteases were present than in the secretory stage of enamel formation. Less digestion of gelatin substrate occurred in several proteases found in the fluorosed maturation-stage enamel as compared with the control maturation-stage enamel. This suggests that the amount of protease secreted or the activity of the proteases may be altered in fluorosed maturation-stage enamel.

Relative Levels of mRNA Encoding Enamel Proteins in Enamel Organ Epithelia and Odontoblasts

2003 ◽  
Vol 82 (12) ◽  
pp. 982-986 ◽  
Author(s):  
T. Nagano ◽  
S. Oida ◽  
H. Ando ◽  
K. Gomi ◽  
T. Arai ◽  
...  
Keyword(s):  
Tooth Enamel ◽  
Structural Proteins ◽  
Enamel Organ ◽  
Maturation Stage ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Enamel Protein ◽  
Enamel Proteins ◽  
Enamel Layer

Amelogenin, enamelin, sheathlin (ameloblastin/ amelin), enamelysin (MMP-20), and KLK4 (EMSP-1) are the major structural proteins and proteinases in developing tooth enamel. Recently, odontoblasts were reported to express amelogenin, the most abundant enamel protein. In this study, we hypothesized that odontoblasts express all enamel proteins and proteases, and we measured their relative mRNA levels in enamel organ epithelia and odontoblasts associated with porcine secretory- and maturation-stage enamel by RT-PCR, using a LightCycler instrument. The results showed that amelogenin mRNA in secretory-stage EOE is 320-fold higher than in odontoblasts beneath secretory-stage enamel, and over 20,000-fold higher than in odontoblasts under maturation-stage enamel. Similar results were obtained for enamelin and sheathlin. Enamelysin mRNA levels were equivalent in these two tissues, while KLK4 mRNA was higher in odontoblasts than in secretory-stage EOE. These results support the conclusion that odontoblasts are involved in the formation of the enamel layer adjacent to enamel-dentin junction.

Alteration of Enamel Proteins in Hypomaturation Amelogenesis Imperfecta

1989 ◽  
Vol 68 (9) ◽  
pp. 1328-1330 ◽  
Author(s):  
J.T. Wright ◽  
W.T. Butler
Keyword(s):  
Amino Acid ◽  
Autosomal Recessive ◽  
Amino Acid Profile ◽  
Amelogenesis Imperfecta ◽  
Healthy Controls ◽  
Diverse Group ◽  
Primary Defect ◽  
Autosomal Recessive Condition ◽  
Enamel Protein ◽  
Enamel Proteins

Amelogenesis imperfecta (AI) is a diverse group of disorders that affects primarily the enamel of teeth through a number of developmental processes. The purpose of this study was to characterize the enamel proteins in normal enamel and in hypomaturation AI enamel. Impacted teeth, which were at similar stages of development, were obtained for analysis from an individual with Al and from normal healthy controls. Evaluation of the amino acid profile and quantity of organic material collected showed that there was an excess of enamel protein material that had an amelogenin-like amino acid profile in mature hypomaturation AI enamel. The AI enamel protein content was 5%, while the control enamel had 0.1% protein (by weight). These findings indicate that the maturation process had been altered in this type of AI, and that maturation did not progress beyond the initial stages of secondary mineralization. Since this disorder is inherited as an autosomal recessive condition, it seems likely that the primary defect involves an abnormality in the mechanism for protein removal in enamel maturation.

scholarly journals Premature Stop Codon in MMP20 Causing Amelogenesis Imperfecta

2008 ◽  
Vol 87 (1) ◽  
pp. 56-59 ◽  
Author(s):  
P. Papagerakis ◽  
H.-K. Lin ◽  
K.Y. Lee ◽  
Y. Hu ◽  
J.P. Simmer ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Proteolytic Enzymes ◽  
Stop Codon ◽  
Translation Termination ◽  
Premature Stop Codon ◽  
Dental Enamel ◽  
Amino Acid Position ◽  
Amelogenesis Imperfecta ◽  
Exon 1 ◽  
Kallikrein 4

Proteolytic enzymes are necessary for the mineralization of dental enamel during development, and mutations in the kallikrein 4 ( KLK4) and enamelysin ( MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only one KLK4 and two MMP20 mutations have been reported. We have identified an ARAI-causing point mutation (c.102G>A, g.102G>A, and p.W34X) in exon 1 of MMP20 in a proband with autosomal-recessive hypoplastic-hypomaturation amelogenesis imperfecta. The G to A transition changes the tryptophan (W) codon (TGG) at amino acid position 34 into a translation termination (X) codon (TGA). No disease-causing sequence variations were detected in KLK4. The affected enamel is thin, with mild spacing in the anterior dentition. The enamel layer is hypomineralized, does not contrast with dentin on radiographs, and tends to chip away from the underlying dentin. An intrinsic yellowish pigmentation is evident, even during eruption. The phenotype supports current ideas concerning the function of enamelysin.

Na-K-ATPase in the Enamel Organ: Localization and Possible Roles in Enamel Formation

1987 ◽  
Vol 1 (2) ◽  
pp. 267-275 ◽  
Author(s):  
P.R. Garant ◽  
T. Sasaki ◽  
P.E. Colflesh
Keyword(s):  
Plasma Membranes ◽  
Organic Matrix ◽  
Enamel Organ ◽  
Maturation Stage ◽  
Enamel Formation ◽  
Morphological Alterations ◽  
Maturation Stages ◽  
Delayed Maturation ◽  
The One

Ouabain-sensitive, K-dependent p-nitrophenyl phosphatase (p-NPPase) activity was localized ultra-Ocytochemically in the lateral plasma membranes of secretory ameloblasts and the stratum intermedium and principally in the papillary layer cells of aldehyde-fixed rat incisor enamel organs by the one-step lead method. Daily intraperitoneal injection of ouabain (250 μg, 500 μg, and 1 mg/100 g body weight) for two weeks reduced p-NPPase activity in the enamel organ cells. However, the degree to which this activity was reduced appeared to vary among the experimental animals. Addition of ouabain to the cytochemical incubation medium completely inhibited p-NPPase activity in the tissues. Although long-term ouabain injection did not result in any morphological alterations of the enamel organ cells, it caused, in part, an appearance of electron-dense, homogeneous matrix-like substances (MS) in the extracellular spaces of the ameloblast layers at both the secretion and maturation stages. In addition, long-term ouabain injection appeared to have resulted in delayed maturation of enamel as measured by energy-dispersive x-ray analysis of Ca and P in surface enamel. These results suggest that Na-K-ATPase of enamel organ cells may participate in the net flow (removal) of organic matrix components and water from the enamel during the maturation stage of enamel formation. It is suggested that this flow is maintained by local osmotic gradients generated by Na-K-ATPase within the papillary layer.

Decreased Mineral Content in MMP-20 Null Mouse Enamel is Prominent During the Maturation Stage

2004 ◽  
Vol 83 (12) ◽  
pp. 909-913 ◽  
Author(s):  
J.D. Bartlett ◽  
E. Beniash ◽  
D.H. Lee ◽  
C.E. Smith
Keyword(s):  
Matrix Metalloproteinase ◽  
Physical Properties ◽  
Mineral Content ◽  
Developmental Stages ◽  
Weight Percent ◽  
Maturation Stage ◽  
Null Mouse ◽  
Kallikrein 4 ◽  
Enamel Proteins

During enamel development, matrix metalloproteinase-20 (MMP-20, enamelysin) is expressed early during the secretory stage as the enamel thickens, and kallikrein-4 (KLK-4, EMSP1) is expressed later during the maturation stage as the enamel hardens. Thus, we investigated whether the physical properties of the secretory-/maturation-stage MMP-20 null enamel were significantly different from those of controls. We demonstrated that although, in relative terms, the weight percent of mature mineral in the MMP-20 null mouse enamel was only 7–16% less than that in controls, overall the enamel mineral was reduced by about 50%, and its hardness was decreased by 37%. Percent mineral content by weight was assessed at 3 different developmental stages. Remarkably, the biggest difference in mineral content between MMP-20 null and controls occurred in the nearly mature enamel, when MMP-20 is normally no longer expressed. This suggests that MMP-20 acts either directly or indirectly to facilitate the removal of maturation-stage enamel proteins.

scholarly journals Enamelin and Autosomal-dominant Amelogenesis Imperfecta

2003 ◽  
Vol 14 (6) ◽  
pp. 387-398 ◽  
Author(s):  
J.C.-C. Hu ◽  
Y. Yamakoshi
Keyword(s):  
Autosomal Dominant ◽  
Dental Enamel ◽  
Severe Form ◽  
Amelogenesis Imperfecta ◽  
Post Translational Modifications ◽  
Enamel Protein ◽  
Enamel Proteins ◽  
Temporal And Spatial ◽  
Secretory Products

Dental enamel forms as a progressively thickening extracellular layer by the action of proteins secreted by ameloblasts. The most abundant enamel protein is amelogenin, which is expressed primarily from a gene on the X-chromosome (AMELX). The two most abundant non-amelogenin enamel proteins are ameloblastin and enamelin, which are expressed from the AMBN and ENAM genes, respectively. The human AMBN and ENAM genes are located on chromosome 4q13.2. The major secretory products of the human AMELX, AMBN, and ENAM genes have 175, 421, and 1103 amino acids, respectively, and are all post-translationally modified, secreted, and processed by proteases. Mutations in AMELX have been shown to cause X-linked amelogenesis imperfecta (AI), which accounts for 5% of AI cases. Mutations in ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that accounts for 27% of AI cases in Sweden. The discovery of mutations in the ENAM gene in AI kindreds proved that enamelin is critical for proper dental enamel formation and that it plays a role in human disease. Here we review how enamelin was discovered, what is known about enamelin protein structure, post-translational modifications, processing by proteases, and its potentially important functional properties such as its affinity for hydroxyapatite and influence on crystal growth in vitro. The primary structures of human, porcine, mouse, and rat enamelin are compared, and the human enamelin gene, its structure, chromosomal localization, temporal and spatial patterns of expression, and its role in the etiology of amelogenesis imperfecta are discussed.

scholarly journals Proteinases in Developing Dental Enamel

1999 ◽  
Vol 10 (4) ◽  
pp. 425-441 ◽  
Author(s):  
J.D. Bartlett ◽  
J.P. Simmer
Keyword(s):  
Proteinase Inhibitors ◽  
Dental Enamel ◽  
Serine Proteinase ◽  
Organic Matrix ◽  
Enamel Organ ◽  
Maturation Stage ◽  
Enamel Matrix ◽  
Enamel Matrix Proteins ◽  
Early Maturation

For almost three decades, proteinases have been known to reside within developing dental enamel. However, identification and characterization of these proteinases have been slow and difficult, because they are present in very small quantities and they are difficult to purify directly from the mineralizing enamel. Enamel matrix proteins such as amelogenin, ameloblastin, and enamelin are cleaved by proteinases soon after they are secreted, and their cleavage products accumulate in the deeper, more mature enamel layers, while the full-length proteins are observed only at the surface. These results suggest that proteinases are necessary for "activating" enamel proteins so the parent proteins and their cleavage products may perform different functions. A novel matrix metalloproteinase named enamelysin (MMP-20) was recently cloned from tooth tissues and was later shown to localize primarily within the most recently formed enamel. Furthermore, recombinant porcine enamelysin was demonstrated to cleave recombinant porcine amelogenin at virtually all of the sites that have previously been described in vivo. Therefore, enamelysin is at least one enzyme that may be important during early enamel development. As enamel development progresses to the later stages, a profound decrease in the enamel protein content is observed. Proteinases have traditionally been assumed to degrade the organic matrix prior to its removal from the enamel. Recently, a novel serine proteinase named enamel matrix serine proteinase-1 (EMSP1) was cloned from enamel organ epithelia. EMSP1 localizes primarily to the early maturation stage enamel and may, therefore, be involved in the degradation of proteins prior to their removal from the maturing enamel. Other, as yet unidentified, proteinases and proteinase inhibitors are almost certainly present within the forming enamel and await discovery.

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