Arja M. Kullaa

The defence architecture of the superficial cells of the oral mucosa

The oral epithelium together with the saliva and its components forms a complex structure which is the first line of defence in the oral cavity. The surface of superficial cells of the oral epithelium contains ridge-like folds, microplicae (MPL), which are typical of the surfaces of areas covered with protective mucus. The role of MPL seen on the upper surface of the oral epithelial cells is still unknown. The salivary mucus gel performs a protective diffusion membrane against harmful substances and this membrane is built up by epithelial cells covered by a highly hydrated and viscous gel, where mucins constitute the scaffold. The interaction between the MPL-structure and the mucins is shown in cornea, so that mucins are expressed on the tips of the MPL of the epithelial cells. We hypothesized that the MPL architecture of oral superficial epithelial cells provides the underlying basis for mucinss protective function as well as in ocular surface. The salivary mucous barrier is required to protect the superficial cells and the MPL-structure together with membrane anchored mucin binding protein (MBP) forms the ground to this mucous barrier. So, oral mucosal barrier complex (OMBC) contains both the MBP-mucin - complex and the MPL-structure of the superficial cells. In the future, studies of the alterations of the salivary mucins and that of the MPL-structure may yield therapeutic opportunities for burning mouth syndrome and perhaps for mucositis causing by irradiation. Focus on cell surface microplication and mucins in oral mucosal biology and oral mucosal diseases is a promising avenue for future research in several ways.

Microstructure of the Superficial Epithelial Cells of the Human Oral Mucosa

Abstract Background: The apical cell membrane of the oral mucosa adjacent to the saliva interface is thrown into membrane folds, termed microplicae (MPL) with variation in morphology. The present study classifies morphological changes undergone by MPL into qualitative and quantitative categories. Material and Methods: Oral mucosal specimens were obtained from 32 healthy patients. Half of each specimen was prepared routinely for light microscopy, and the other part for scanning and transmission electron microscopy. Different measurements of cell structure were presented: the density of MPL, the width and height of MPL, the width of furrows between two adjacent MPL and the distance of the centre of MPL. Morphometric measurements were obtained using a semiautomatic ImageJ analysis software (W Rasband, National Institutes of Health, Bethesda, MD). Results: Parallel and branching MPL was common observation in the area of lining mucosa and in the tongue between the filiform papillae. The density of MPL was higher in the cells of the buccal mucosa than in the cells of the tongue, 43.69 + 11.43% and 31.68 + 10.32%, respectively. The difference was significant (p < 0.001). The width of MPL was 0.16 µm in cells of the buccal mucosa and 0.12 µm in cells of the tongue. Conclusions: Our findings support the idea that MPL structure is a determining factor for the functionality of the oral epithelium since the values of the MPL were kept relatively stable. The role of MPL structure of the oral mucosal cells is discussed.

Microstructure of Oral Epithelial Cells as an Underlying Basis for Salivary Mucosal Pellicle

Abstract Background: Salivary mucosal pellicle forms the structural basis of the local innate immune defense mechanism of the oral mucosa. At the surface of the oral mucosa, the apical cell membrane adjacent to the saliva interface contains short membrane folds, termed microplicae (MPL). This MPL structure of oral epithelial cells and its function as a basis to the salivary mucosal pellicle is unclear. In this preliminary study, we describe the ultrastructural morphology of cell membrane of superficial cells of the oral mucosa and study the membrane-associated mucins (MAMs), MUC1 and MUC4, with immunohistological methods. Materials and methods: Oral mucosal specimens were obtained from six healthy patients. Half of each specimen was prepared routinely for light microscopy, and the other part for scanning and transmission electron microscopy. The presence of MUC1 and MUC4 were studied by immunohistochemical methods in oral mucosal specimens. Results: Morphologically, the cell membrane of MPL is partly discontinuous and membrane-associated molecules extrude from the cell membrane. MUC1 expression was detected in the superficial part of the buccal epithelium, while MUC4 had no expression in the oral squamous epithelium. Conclusions: The novel of this study is that the membrane-tethered molecules seem to occur onto the cell membrane of the superficial epithelial cells of the oral mucosa. Furthermore, the stratified squamous epithelium of the buccal mucosa produces MUC1 for the surface-saliva pellicle interface. The interaction between MPL structure, MUC1 mucin, and salivary mucosal pellicle is discussed.

Recent advances in optical diagnosis of oral cancers: review and future perspectives

Optical diagnosis techniques offer several advantages over traditional approaches, including objectivity, speed, and cost, and these label‐free, noninvasive methods have the potential to change the future workflow of cancer management. The oral cavity is particularly accessible and, thus, such methods may serve as alternate/adjunct tools to traditional methods. Recently, in vivo human clinical studies have been initiated with a view to clinical translation of such technologies. A comprehensive review of optical methods in oral cancer diagnosis is presented. After an introduction to the epidemiology and etiological factors associated with oral cancers currently used, diagnostic methods and their limitations are presented. A thorough review of fluorescence, infrared absorption, and Raman spectroscopic methods in oral cancer diagnosis is presented. The applicability of minimally invasive methods based on serum/saliva is also discussed. The review concludes with a discussion on future demands and scope of developments from a clinical point of view.

Metabolic Profiling of Saliva in Patients with Primary SjögrenâÂÂs syndrome

Objective: To investigate the feasibility of 1 H-NMR spectroscopy for metabolic profiling of human saliva samples and to determine whether the concentration of certain salivary metabolites, mainly representing small organic acids and amino acids, differ between patients with primary Sjogren´s syndrome (pSS) and healthy controls. Methods: Stimulated whole-mouth saliva (SWMS) was collected from female pSS patients (n =15, all fulfilling the revised European Community proposed criteria). Salivary flow rate was immediately determined, samples were then frozen and subsequently analyzed by 1 H-NMR spectroscopy in comparison with samples collected from healthy individuals (n=15). Results: From each sample, up to 24 metabolites could be identified and quantified. Choline and taurine concentrations were very significantly higher in the pSS patients compared to healthy controls (p<0.001), but their concentrations correlated negatively with salivary flow rate. Alanine and glycine concentrations were significantly higher (p=0.004, p=0.007, respectively), whereas butyrate (p= 0.034), phenylalanine (p=0.026) and proline (p=0.032) were only slightly higher in pSS saliva samples than in controls. Conclusions: NMR spectroscopy has a potential for quantitative metabolic profiling of saliva samples. NMR spectroscopy is suitable for the analysis of NAAs in saliva and it can bypass the other methods, which are normally suitable for analysis of just one metabolite.

Surface Morphology of Superficial Cells in Irradiated Oral Mucosa: An Experimental Study in Beagle Dog

Abstract Objectives: The aim of the present study is to investigate if radiation induces changes in the superficial cells of the oral mucosa and secondly to describe morphological characteristics of the cell surface structure by scanning electron microscopy (SEM). Materials and methods: Ten beagle dogs aged 1–2 years were used in this study. One side of each mandible was irradiated in two sessions, each lasting 1 week. The total dosage was 40 Gy (Group A; 5 dogs) and 50 Gy (Group B; 5 dogs), in five fractions of 4 Gy. The other side of mandible (non-irradiated) served as a control. The specimen was harvested with a scalpel from the alveolar mucosa of the irradiated area 1 year after irradiation and studied with SEM. Results: In the control side, the surface structure of the cell contains straight parallel or branched microplicae (MPL), which were equally spaced over the cell surfaces. Discontinuous and short MPL were typical cell structure of irradiated mucosa. In 50 Gy group, the surface structure of epithelial cell was pitted and the cell boundaries were thick. Conclusions: The novelty of the present study is that radiation disrupts superficial cells of the oral mucosa. The role of the MPL structure of the superficial cells in mucositis development is discussed.

Oral mucosal epithelial cells express the membrane anchored mucin MUC1

OBJECTIVE The presence of a stable salivary pellicle (SP) is essential to provide a wet surface for the oral mucosal epithelia. The oral mucosa is covered by the SP which is suggested to be a mixed film of both salivary and epithelial components. Our aim was to analyse the presence of membrane-anchored mucin MUC1 in the oral mucosal epithelia. DESING The presence of MUC1 was studied by immunohistochemical and immunoelectron microscopical methods in 19 buccal mucosal specimens. The localization and intensity of the epithelial expression were analyzed. RESULTS Strong staining of MUC1 was found in the epithelial cells of intermediate and superficial layers. Some basal cells were shown faint expression. In the intermediate and superficial layers, the MUC1 expression was seen mainly on the upper cell surface. Furthermore, the expression of MUC1 was noted in the cytoplasm near the nucleus and in the rough granules. By electron microscopy, extracellular domain of membrane-anchored molecules extruded about 15-30nm above the cell surface in the apical cells of the oral epithelium. Immunoelectron microscopic examination shows that MUC1 is mainly localized in the plasma membrane of epithelial cells and also in small vesicles (75-100nm) just below the plasma membrane. CONCLUSION The membrane-anchored MUC1 is expressed in the superficial layer of the oral mucosal epithelium, especially on the upper surface of epithelial cells. MUCI may be the anchoring protein of the salivary pellicle stabilization.

Fissured tongue: a sign of tongue edema?

Fissured tongue (FT) is a condition frequently seen in the general population. Clinically, FT is characterized by grooves that vary in depth and are noted along the dorsal and/or dorsolateral aspects of the tongue. Furthermore, FT presents many enlarged, smooth filiform papillae and subepithelial inflammatory infiltration. Despite of many studies, the etiology of FT remains obscure. FT is believed to be a congenital anomaly associated with several disorders and with geographic tongue (GT). We hypothesize that FT is not a congenital anomaly, and FT with swollen filiform papillae may represent edema in the subepithelial tissue of the tongue. According to the literature, the difference in prevalence among different age groups indicates that FT is not a congenital disorder. FT appears to occur more commonly in adults, and it is very rare or not at all in children younger than 10 years old. An association between FT and GT is well established in the literature, supporting the results of previous authors suggesting that FT might be a consequence of GT. The most remarkable finding in the region of swollen papillae of FT samples has been the subepithelial infiltrates of polymorphonuclear leucocytes and lymphocytes causing the subepithelial edema. The clinically visible grooves and large edematic papillae clustered on the region of the fissures might be caused by the inflammation and edema underneath the epithelium. In the future, FT and GT must be researched together as two different entities of the same disease so that GT is a prestage of FT. The diagnosis of FT must be taken to consideration whether the tongue surface have smooth and swollen papillae or normal-appearing filiform papillae.

Microplicae - Specialized Surface Structure of Epithelial Cells of Wet-Surfaced Oral Mucosa

ABSTRACT The surface structure of the superficial cells of the oral mucosa is decorated with numerous membrane ridges, termed microplicae (MPLs). The MPL structure is typical of the epithelial surfaces that are covered with protective mucus. Cell membrane MPLs are no longer seen as passive consequences of cellular activity. The interaction between MPLs and the mucins has been demonstrated, however the role of MPL structure seen on the upper surface of the oral epithelial cells is speculative. The cell surface is of potentially great significance, as it harbors many markers for refined prognosis and targets for oral mucosal diseases and cancer therapy. With these aspects in mind, we conducted the present review of the MPL structure and function in order to form the basis for further studies of MPLs of the oral epithelial cells.

Altered expression of hyaluronan, HAS1‐2, and HYAL1‐2 in oral lichen planus

BACKGROUND Oral lichen planus (OLP) is an immune-mediated mucosal disease of unclear etiology and of unresolved pathogenesis. Hyaluronan (HA) is an extracellular matrix glycosaminoglycan involved in inflammation and tumor progression. However, its presence in OLP has not been reported. We therefore aimed to study the immunohistochemical expression of HA, its receptor CD44, hyaluronan synthases (HAS1-3), and hyaluronidases (HYAL1-2) in OLP. METHODS The presence of HA, CD44, HAS1-3, and HYAL1-2 was studied by immunohistochemical methods in 55 OLP and 23 control oral mucosal specimens (CTR). The localization, intensity, and differences of the epithelial expression between OLP and CTRs were analyzed. RESULTS HA and CD44 were found on cell membranes in the epithelial basal and intermediate layers in CTR and OLP specimens. The HA staining intensity was stronger in the basal layer of the epithelium in OLP than in CTRs (P < 0.001). HAS1 (P = 0.001) and HAS2 (P < 0.001) showed stronger staining in the basal and weaker staining in the superficial (P < 0.001) epithelial layers in OLP than in CTRs. The immunostaining of HAS3 was low in both OLP and CTRs. Positive HYAL1 and HYAL2 staining were mainly found in the basal and intermediate epithelial layers, and their intensities were significantly increased in OLP, except HYAL 2 in the intermediate epithelial layer. CONCLUSIONS HA, HAS1-2, and HYAL1-2 have altered expression in OLP compared to CTRs and may therefore have a role in OLP pathogenesis.