The pathological events leading to the destruction of the periodontium during inflammatory periodontal diseases are likely to represent complex interactions involving an imbalance in enzymic and non‐enzymic degradative mechanisms. This paper aims to review the increasing body of evidence implicating reactive oxygen species (ROS), derived from many metabolic sources, in the pathogenesis of periodontal tissue destruction. ROS are generated predominantly by polymorphonuclear leukocytes (PMN) during an inflammatory response and are regarded as being highly destructive in nature. The detection of ROS oxidation products, the elevation of iron and copper ions, which catalyse the production of the most reactive radical species, and the identification of an imbalance in the oxidant/antioxidant activity within periodontal pockets, suggests a significant role for ROS in periodontal tissue destruction. In vitro studies have shown that ROS are capable of degrading a number of extracellular matrix components including proteoglycans, resulting in the modification of amino acid functional groups, leading to fragmentation of the core protein, whilst the constituent glycosaminoglycan chains undergo limited depolymerisation. The identification and characterisation of connective tissue metabolites in gingival crevicular fluid (GCF) resulting from the degradation of periodontal tissues, notably alveolar bone, provides further evidence for a role for ROS in tissue destruction associated with inflammatory periodontal diseases.

The predominant proteoglycans present in predentin and dentin are the chondroitin-sulphate-rich decorin and biglycan and the keratan-sulphate-rich lumican and fibromodulin. These are small, interstitial, leucine-rich proteoglycans which have recently been shown to exist in gradients across the predentin. Antibodies recognizing chondroitin sulphate show a decreasing gradient from the pulpal aspect toward the mineralizing front, the converse being true for keratan sulphate. Antidecorin shows an increase toward the mineralization front. Evidence from biochemical, autoradiographic, and immunohistochemical studies implies that such changes may be brought about by gradients of metalloproteinases. This offers the possibility that the proteoglycans organize the collagen network for receipt of phosphoproteins and phospholipids, the former being evident only at the onset of dentin formation. The suggestion is raised that glycosaminoglycan-depleted leucine-rich protein cores act as sequester points for receipt of phosphoproteins in particular. The rigid, spatially oriented glycosaminoglycan chains on decorin and biglycan are known to bind calcium and may feature directly in mineral initiation.Key words. Dentinogenesis, proteoglycans, phosphoconjugates, metalloproteinases, mineralization.(I) Introduction Jn recent years, there has been a wealth of new information on the group of non-collagenous glycoconjugates present in the extracellular matrix of most connective tissues, termed proteoglycans (PGs). These molecules are deemed to play structural and metabolic functional roles in both the soft and mineralized tissues of the body and are present in a wide variety of non-vertebrate and vertebrate species.Their presence in mineralized tissues, such as bone, has been evident for some time. Although the presence of PGs in predentin and, to a lesser extent, in dentin is well-established, it is only with the advent of contemporary biochemical and immunohistochemical procedures that their speciation, ultrastructural distribution, and possible biological roles in dentinogenesis are beginning to be elucidated.Within the last decade, there have been few reviews specifically addressing the function of PGs in relation to dentinogenesis. Research in this field has borrowed much of its knowledge from connective tissues in general, particularly the work on the aggregating PGs, such as aggrecan, present in cartilage. It The aspect of gradient distribution will be described in detail later and is of major significance, since it offers a functionality for such molecules during the structural transition of the extracellular matrix (ECM) of predentin, leading to the correct spatial assembly of the collagenous-non-coliagenous scaffold as a prelude for mineral deposition. For this reason, the review wili also deal with recent work on the potential of metalioproteinases (MMPs) to bring about such transition and the presence of phosphoprotein in dentin specifically hnked to mineralization. The absence of phosphoprotein from predentin an...

The effect of reactive oxygen species (ROS), generated by in vitro stimulation of isolated PMN upon the main GAG components of mineralised and non-mineralised connective tissues was investigated. PMN were isolated from whole blood and the production of the ROS superoxide (O2.-) and hydroxyl radicals (.OH) was stimulated by the addition of phorbol myristyl acetate (PMA) and PMA/FeCl3-EDTA chelate respectively and their production assessed over a 24 h period. The glycosaminoglycans (GAG), hyaluronan, chondroitin 4-sulphate and dermatan sulphate, were exposed to the ROS fluxes, incubated at 37 degrees C for 1 h and 24 h. GAG fragmentation was examined by gel exclusion chromatography and modification to hexuronic acid and hexosamine residues determined. Stimulation of PMN with PMA resulted in a burst of O2.- production for 1 h, which was sustained at a reduced level for 24 h. Fragmentation of GAG was observed for all GAG examined. Modification to the GAG was evident, with hyaluronan being more susceptible to loss of GAG residues than sulphated GAG. Modification of sugar residues increased with the incubation time and loss of the hexuronic acid residues was greater than loss of hexosamine residues. Addition of FeCl3-EDTA chelate, which led to the generation of .OH and was sustained over the 24 h period, demonstrated similar trends of GAG modification although increased degradation and loss of hexosamine and hexuronic acid were observed. GAG chains are constituents of PGs and their modification is likely to affect the function of these macromolecules and be of importance in considering the pathogenesis of inflammatory diseases, including periodontal diseases.

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