Abstract
Odontoblasts and pulp stroma cells are embedded within supramolecular networks of extracellular matrix (ECM). Fibrillin microfibrils and associated proteins are crucial constituents of these networks, serving as contextual scaffolds to regulate tissue development and homeostasis by providing both structural and mechanical properties and sequestering growth factors of the TGF-β superfamily. EMILIN-1, -2, and -3 are microfibril-associated glycoproteins known to modulate cell behaviour, growth factor activity, and ECM assembly. So far their expression in the various cells of the dentin-pulp complex during development, in the adult stage, and during inflammation has not been investigated. Confocal immunofluorescence microscopy and western blot analysis of developing and adult mouse molars and incisors revealed an abundant presence of EMILINs in the entire dental papilla, at early developmental stages. Later in development the signal intensity for EMILIN-3 decreases, while EMILIN-1 and -2 staining appears to increase in the pre-dentin and in the ECM surrounding odontoblasts. Our data also demonstrate new specific interactions of EMILINs with fibulins in the dentin enamel junction. Interestingly, in dentin caries lesions the signal for EMILIN-3 was significantly increased in inflamed odontoblasts. Overall our findings point for the first time to a role of EMILINs in dentinogenesis, pulp biology, and inflammation.
Highlights
Odontoblasts and pulp stroma cells are embedded within supramolecular networks of extracellular matrix (ECM)
While EMILIN-1 and EMILIN-3 were found in adjacent mesenchymal tissues, EMILIN-2 distribution was restricted to the condensed mesenchyme of the dental papilla (Fig. 1A)
In newborn incisors EMILIN-2 was evenly stained in the entire pulp mesenchyme, whereas EMILIN-1 and in particular EMILIN-3 were enriched in the region of the mesenchymal stem cell niche (Fig. 1D)
Summary
Odontoblasts and pulp stroma cells are embedded within supramolecular networks of extracellular matrix (ECM). EMILIN-1, -2, and -3 are microfibril-associated glycoproteins known to modulate cell behaviour, growth factor activity, and ECM assembly Their expression in the various cells of the dentin-pulp complex during development, in the adult stage, and during inflammation has not been investigated. Our previous in vivo and in vitro studies in skin showed that EMILIN-1 ECM incorporation depends on the presence of FMF and not vice versa[36], illustrating tissue specific differences in ECM assembly and structure Despite their important function to modulate the activity of growth factors known to be essential for odontoblast differentiation, mineralization and regeneration, no information about the spatio-temporal localization of EMILINs and their functional interactions in the dental pulp is known. We defined novel functional interactions with the DEJ components fibulin-1 and -2 and demonstrated co-localization with BM remnants within the junction
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