Dipeptidyl‐peptidase II and cathepsin B activities in amelogenesis of the rat incisor

Smid, J. R.; Young, William G.; Monsour, P. A.

doi:10.1034/j.1600-0722.2001.00025.x

Cited by 4 publications

(3 citation statements)

References 43 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Forming enamel, however, is over 30% protein (5). Much of the protein is reabsorbed by ameloblasts and degraded in lysosomes (6,7), but extracellular proteases also play a role in matrix protein removal (8 -10).…”

mentioning

confidence: 99%

Hypomaturation Enamel Defects in Klk4 Knockout/LacZ Knockin Mice

Simmer

Lertlam

et al. 2009

Journal of Biological Chemistry

134

184

View full text Add to dashboard Cite

Kallikrein 4 (Klk4) is believed to play an essential role in enamel biomineralization, because defects in KLK4 cause hypomaturation amelogenesis imperfecta. We used gene targeting to generate a knockin mouse that replaces the Klk4 gene sequence, starting at the translation initiation site, with a lacZ reporter gene. Correct targeting of the transgene was confirmed by Southern blot and PCR analyses. Histochemical X-gal (5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside) staining demonstrated expression of ␤-galactosidase in maturation stage ameloblasts. No X-gal staining was observed in secretory stage ameloblasts or in odontoblasts. Retained enamel proteins were observed in the maturation stage enamel of the Klk4 null mouse, but not in the Klk4 heterozygous or wild-type mice. The enamel layer in the Klk4 null mouse was normal in thickness and contained decussating enamel rods but was rapidly abraded following weaning, despite the mice being maintained on soft chow. In function the enamel readily fractured within the initial rod and interrod enamel above the parallel enamel covering the dentinoenamel junction. Despite the lack of Klk4 and the retention of enamel proteins, significant levels of crystal maturation occurred (although delayed), and the enamel achieved a mineral density in some places greater than that detected in bone and dentin. An important finding was that individual enamel crystallites of erupted teeth failed to grow together, interlock, and function as a unit. Instead, individual crystallites seemed to spill out of the enamel when fractured. These results demonstrate that Klk4 is essential for the removal of enamel proteins and the proper maturation of enamel crystals.Dental enamel is composed of highly ordered, very long crystals of calcium hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ). Mature enamel crystallites are about 70 nm wide and 30 nm thick, but are of unmeasurable length (1), probably extending all the way from the dentin layer to the surface of the tooth (2). Enamel crystallites are organized into bundles called rods, with about 10,000 parallel crystals in a rod (3). Each enamel rod is the product of a single ameloblast, the cell type that forms a continuous sheet over the developing enamel and orchestrates its formation. Dental enamel of erupted teeth is ϳ95% mineral (by weight) (4), with most of the non-mineral component being water. Protein comprises Ͻ1% of its weight. Forming enamel, however, is over 30% protein (5). Much of the protein is reabsorbed by ameloblasts and degraded in lysosomes (6, 7), but extracellular proteases also play a role in matrix protein removal (8 -10).Dental enamel formation is divided into secretory, transition, and maturation stages (11,12). During the secretory stage, enamel crystals grow primarily in length. As the crystals extend, the enamel layer expands. Enamel crystallites lengthen along a mineralization front at the secretory surface of the ameloblast cell membrane. There, mineral deposits rapidly on the crystallite tips, and very slowly on their sides...

show abstract

mentioning

confidence: 99%

Hypomaturation Enamel Defects in Klk4 Knockout/LacZ Knockin Mice

Simmer

Lertlam

et al. 2009

Journal of Biological Chemistry

134

184

View full text Add to dashboard Cite

show abstract

“…Cats B, D and L have previously been detected in ameloblasts (Smid, JR et al, 2001; Al Kawas, S et al, 1996; Andujar, MB et al, 1989; Nishikawa, S., 2005), however, identification of Cat K in enamel organ is novel. Cat K is a cysteine protease predominantly expressed in osteoclasts with high expression also seen in ovary, small intestine and colon and at lower levels in heart, skeletal muscle, placenta, lung, prostate, testes, spleen, thymus, kidney, pancreas and liver (Brömme, D., K. Okamoto, 1995).…”

Section: Discussionmentioning

confidence: 98%

“…Cathepsins B, D and L, as well as dipeptidyl peptidase II (DPP II) have previously been identified in ameloblasts (Smid, JR et al, 2001; Al Kawas, S et al, 1996; Andujar, MB et al, 1989; Nishikawa, S., 2005). This study sought to identify previously unidentified lysosomal proteases present during enamel maturation.…”

Section: Introductionmentioning

confidence: 99%

Lysosomal Protease Expression in Mature Enamel

Tye¹,

Lorenz²,

Bartlett³

2008

Cells Tissues Organs

View full text Add to dashboard Cite

The enamel matrix proteins (amelogenin, enamelin and ameloblastin) are degraded by matrix metalloproteinase-20 and kallikrein-4 during enamel development and mature enamel is virtually protein free. The precise mechanism of removal and degradation of the enamel protein cleavage products from the matrix, however, remains poorly understood. It has been proposed that receptor-mediated endocytosis allows for the cleaved proteins to be removed from the matrix during enamel formation and then transported to the lysosome for further degradation. This study aims to identify lysosomal proteases that are present in maturation-stage enamel organ. RNA from first molars of 11-day-old mice was collected and expression was initially assessed by RT-PCR and then quantified by qPCR. The pattern of expression of selected proteases was assessed by immunohistochemical staining of demineralized mouse incisors. With the exception of cathepsin G, all lysosomal proteases assessed were expressed in maturation-stage enamel organ. Identified proteases included cathepsins B, D, F, H, K, L, O, S and Z. Tripeptidyl peptidases I and II as well as dipeptidyl peptidases I, II, III and IV were also found to be expressed. Immunohistochemical staining confirmed that the maturation-stage ameloblasts express cathepsins L and S and tripeptidyl peptidase II. Our results suggest that the ameloblasts are enriched by a large number of lysosomal proteases at maturation that are likely involved in the degradation of the organic matrix.

show abstract