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Background: Collagen type I, proteoglycans (PG) and non-collagenous proteins represent important building blocks of the dentine matrix. While different PGs have been identified in dentine, changes in the distribution of these macromolecules with the progression of caries have been poorly characterized. The aim of this study was to compare the immunolocalization of three small collagen-binding PGs (biglycan, fibromodulin and lumican) as well as collagen (types I and VI) in healthy versus carious dentine.Methods: Longitudinal demineralized sections of extracted teeth were stained with antibodies recognizing specific PG core proteins and collagens, as well as glycosaminoglycans (GAGs) with toluidine blue.Results: In healthy dentine, PGs appeared to be more abundant near the tubule walls and directly under the cusps. Conversely, in carious dentine, specific locations appeared to be more prone to PG degradation than others. These degradation patterns were well correlated with the progression of caries into the tissue, and also appeared to trigger interesting morphological changes in the tissue structure, such as the deformation of dentine tubules near highly infected areas and the lower concentration of PG in tertiary dentine.Conclusions: This study presents new insights into the involvement of PGs in the progression of caries. [ABSTRACT FROM AUTHOR]