Towards a cellular and molecular understanding of periodontics. Cementogenesis revisited.

C U R R E N T C O N C E P T S of plaque-associated inflammatory periodontal disease have been derived to a large extent from histopathologic and electron microscopic descrip­ tions of the lesions. The most common form of plaqueassociated inflammatory periodontal disease appears during childhood or young adulthood and is associated with the presence of microbial plaque on the surfaces of the tee th . 1 , 2 In many cases, the lesion was observed to be confined to the marginal gingiva where it exhibited no overt clinical manifestations, or it was observed as a frequently transient gingivitis. In some individuals, how­ ever, the lesion evolved into a destructive periodontitis leading to degradation of the gingival connective tissue architecture with severe fibrosis, extreme modifications of the junctional epithelium, and appreciable loss of the adjacent alveolar bone. These extensive intracellular and extracellular tissue alterations complement increased pocket formation, tooth mobility, and eventual tooth exfoliation; all of which have been described as charac­ teristic of the advanced stages of this type of periodontal disease. 3 In recent years, attention has been focused increasingly upon the host response and the possibility that destruc­ tive aspects of the host's normal defense mechanisms can function as a major determinant in the pathogenesis of periodontal disease. 4 6 The well-documented fact that the prevalence and extent of periodontal disease actually increased linearly with increasing age 7 may prove to be a direct consequence of intrinsic host-related factors rather than of extrinsic bacterial substances within the dental plaque. The response of the host's defense mechanisms may be significant in determining the pathogenesis of this disease process. In most primates and dogs, lesions of the plaqueassociated inflammatory periodontal disease can be experimentally induced by permitting microbial plaque to accumulate on the surfaces of teeth. Interestingly enough, the specific microbial content of the plaque does not at this point seem to be a relevant factor in the induction of the lesions. ' 9 In some cases the established lesions rapidly evolve (months to several years) into advanced periodontitis exhibiting extensive alveolar bone loss and degradation of the connective tissues. 1 0 The reasons for this extremely rapid progression of soft and hard tissue destruction remain completely obscure. At the present time it is extremely difficult, if not impossi­ ble, to predict which lesions will remain stable over long periods of time (e.g. 2 to 10 years), and which lesions will become aggressive and evolve into rapid degradation of Sharpeys' fibers, alveolar bone and the subsequent loss of teeth. This facet of a multifactorial disease process is a critical problem for future research. Tentatively, there appear to be two essential possibilities: (1) the genesis of a lesion which evolves into an aggressive and destructive disease may be the direct consequence of an activation of the host's immune mechanisms. Available evidence indi­ cates that cell-mediated and humoral hypersensitivity mechanisms can participate significantly in the genesis of an aggressive periodontal d i sease . 1 1 1 4 Alternatively, changes in the plaque microbial flora, rather than in the host's immune response mechanisms, may be of primary importance and causal to the subsequent pathogenesis. It is towards the first possibility that my discussion will present evidence which now suggests that the initiation of acellular cementum is regulated by Hertwig's epithelial root sheath (epithelium). The initial epithelial secretion appears to be "enamel-like" macromolecules which share antigenic determinants in common with enamel proteins. Enamel protein has been found to be an alloantigen and has been demonstrated to produce an alloimmune response. This evidence can now be used to argue, albeit indirectly as yet, that enamel protein is capable of serving as an autoantigen and is a constituent of the acellular cementum extracellular matrix which can provoke an "autoimmune" reaction on the part of the host's immune response. If validated, this conceptual scaffold would provide data towards an understanding of the cellular and molecular biology of the pathogenesis of aggressive periodontal disease.