Perlecan, a Heparan Sulfate Proteoglycan, Is a Major Constituent of the Intraepithelial Stroma Functioning in Tooth Morphogenesis

Perlecan, a heparan sulfate proteoglycan, is one of the major basement membrane macromolecules, plays an important role in cellular growth, differentiation, adhesion,, motility by its interaction with growth factors, cytokines. Recently, perlecan has been localized within the epithelial space in various pathophysiological conditions. As the intraepithelial accumulation of perlecan results in widening of the intercellular space, the most characteristic example of such phenomena is the stellate reticulum of the enamel organ of tooth germs, whose structure, function have been largely unknown. Stellate reticulumlike structures are also found in pathological conditions such as ameloblastoma or oral epithelial dysplasia. The biosynthesis of perlecan has been demonstrated in those epithelial cells,, such peculiar stellate reticulum appearances are shown to be due to intercellular deposits of over-expressed perlecan. However, when perlecan is transgened into mouse epithelial tissue using the keratin 5 promoter, the tooth cannot be formed normally. Thus, a constant over-expression of perlecan interferes with normal development. The time schedule of the intraepithelial expression of perlecan seems to be controlled critically in the process of odontogenesis. In this review article, we address the current views on the structure, function of perlecan acting in the intraepithelial stromal space, with special attention to its role in tooth morphogenesis.