We have determined the patterns of synthesis of cytokeratins and other epithelial marker proteins in the "rests of Malassez" of the periodontium of rabbits and humans, by immunofluorescence microscopy of cryosections prepared from fixed and decalcified rabbit teeth with attached ligament or from manually isolated human periodontal ligaments.
Proteins of the major cell structures characterizing epithelial differentiation are present in Malassez cells: a complex set of cytokeratins as well as desmosomal, hemidesmosomal and basal lamina proteins. In addition, we have shown these cytoskeletal and extracellular matrix structures by electron microscopy. The cytokeratin complement of Malassez cells was found to be highly complex, as 8 of the total of 20 known epithelial cytokeratins were detected (nos. 5, 7, 8, 14, 15, 17, 18, 19). This pattern, together with the presence of the desmosomal cadherins Dsg2 and Dsc2 and the cytoplasmic desmosome plaque-associated protein plakophilin 1, indicates that the cells of the rests of Malassez are derived from the basal cell layer of a stratified squamous epithelium rather than from simple epithelial or neuroendocrine epithelial cells. Our observations show that Malassez cells retain the major characteristics of epithelial cells throughout their differentiation from the root sheath epithelium into the rests of Malassez, even though the surface location and the polar tissue architecture that typify epithelia are lost during this process. From this study we further conclude that the specific cytoskeletal complement of the Malassez cells re- presents an intrinsic gene expression program that neither depends on nor causes the formation of a stratified epithelium. We also compare the specific cytoskeletal features of Malassez cells with those of other persisting epithelial residues and discuss the potential value of these findings in relation to the histogenesis and diagnostic classification of dental and periodontal cysts and tumors.