Connective Tissues of the Periodontium: A Summary of Current Work

Abstract

The connective tissues around the teeth have been studied extensively with regard to their construction, composition, and metabolism under both normal and pathologic conditions. These tissues have served as a model for connective tissues in general, especially in studies aimed at understanding mechanisms regulating normal tissue maintenance and turnover, and changes which occur as disease develops. In normal gingiva, the proportions of the various collagen types are very similar to those in skin, but the molecules appear to be tailored differently. After the teeth are removed, the gingiva becomes converted to mucosa, and the characteristics of the collagens change. As periodontitis develops, significant qualitative and quantitative changes occur. The rate of collagen production and degradation are greatly increased, while the total amount of collagen decreases. The amount of type V collagen increases about seven-fold, and an entirely new collagen, the type I trimer, appears which may account for up to 29% of the total collagen present. The types and proportions of collagens synthesized by fibroblasts from normal gingiva are very similar to those found in the normal tissue. Fibroblasts derived from inflamed gingiva are a unique phenotype in that they continue to synthesize the type I trimer in vitro, and it may account for up to 14% of the total collagen produced in some cultures. Cells obtained from explants of tissue from individuals with drug-induced or spontaneously occurring gingival hyperplasia are also unusual; they synthesize abnormal amounts of protein and collagen, and these characteristics persist indefinitely in vitro. Fibroblast functions are regulated by environmental ligands, some found in blood platelets and plasma, and others synthesized and secreted by infiltrating leukocytes. For example, substances present in serum cause the cells to decrease their production of type III collagen, while greatly increasing production of type V. The C1 component of complement is a mitogen for a subpopulation of gingival fibroblasts, and the cells display binding sites for the collagenous region of the C1q subcomponent of C1. Activated lymphoid cells release a factor or factors which inhibit cell growth by preventing cells in the G₀ or G₁ stage of the cell cycle from leaving, and by preventing division of cells in G₂. In these cells, total protein synthesis is affected only slightly, but collagen synthesis is greatly inhibited; in addition, the production of an unidentified protein of Mr approximately 70,000-daltons appears to be halted. Activated macrophages also produce substances which affect fibroblasts, among which are the prostaglandins. PGE₂ interacts with a subpopulation of gingival fibroblasts in culture to inhibit membrane transport, protein synthesis, and growth without apparent effects on the remaining cells. In contrast, epidermal growth factor enhances growth and total protein production, without affecting the amount of collagen synthesized. The mechanisms underlying the observed pathologic alterations are complex and not well understood. Differential degradation by collagenase and other enzymes present in inflamed tissues may account in part for the changes in the quantity and ratios of the collagens. The amounts and types of regulatory molecules in inflamed and non-inflamed tissue differ greatly, and this may alter fibroblast growth and synthesis activities. However, these processes cannot account for the presence of unusual phenotypes in diseased tissue, nor for their persistence indefinitely in culture. To account for these observations, we have proposed that human fibroblasts are genetically heterogeneous, that a process of clonal selection governed by environmental ligands which inhibit or enhance growth rates occurs, and that the tissue composition observed in both normal and diseased tissue is in part a consequence of the mixtures of clones present.