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7
The Structure andFunction ofthe Oral Mucosa
Gargi Sarode and Sachin Sarode
Department of Oral and Maxillofacial Pathology, Dr. D. Y. Patil Dental College and Hospital, Pune, India
7.1 Introduction
The term mucosa (mucous membrane) refers to the moist lining of the gastrointestinal tract, nasal tract and other cavities of the body that interconnect with the external environment. This lining is denoted as the oral mucosa (oral mucous membrane) in the oral cavity(1). It is a membrane that is distinctively wet and soft and extends anteriorly from the vermilion border of the lips to the palatopharyngeal folds posteriorly. Oral mucosa is lined by stratified squamous epithelium. The epithelium is a structured, avascular and semipermeable tissue. The thickness and keratinisation differ as per the oral site and the tissue’s functional and mechanical necessities in that area(2).
The oral mucosa has a variety of functions. Broadly, these functions can be listed as protective (physical barrier function), immunological surveillance and those related to taste, sensation (touch, pressure and pain) and the production of speech, reflexes (swallowing and gagging) and salivation.
The stratified squamous epithelium of the oral mucosa is classified into keratinised or non­keratinised epithelium. The keratinised epithelium is further classified into para- keratinised or ortho- keratinised. The thickness and level of keratinisation vary depending on the oral sites and the tissue’s functional and mechanical demands. Beneath the epithelium is a superficial connec­tive called lamina propria, separated by a basement membrane. Deeper dense connective tissue is called submucosa (Figure7.1). In certain areas, there is no submucosa, and thus the lamina pro­pria is directly bound to either underlying bone or muscle(2). Submucosa contains neurovascular tissue, lymphatics, adipose tissue and minor salivary glands.
7.2 Classification
The oral mucosa can be classified into three types based on their histological, functional and regional characteristics. Types include lining or movable mucosa, masticatory and specialised mucosa (Table7.1).
Pathological Basis of Oral and Maxillofacial Diseases, First Edition. Edited by S. R. Prabhu, Syed Ali Khurram, Omar Kujan and Merva Soluk Tekkesin. © 2025 John Wiley & Sons Ltd. Published 2025 by John Wiley & Sons Ltd.
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Epithelium
Lamina propria
Submucosa
7.2 Classification
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Periosteum
Bone
Figure7.1 Main tissue components of the oral mucosa. Source: With permission of Pocket Dentistry.
Table7.1 Types of oral mucosa(1, 2).
Histological type of
Types of OMM
Lining/moveable Non- keratinised
epithelium Functions Location (region)
stratified squamous
Flexibility is required for holding water, whistling, blowing air, etc.
Soft palate, buccal, labial and alveolar mucosa, floor of the mouth and vestibular fornix
Masticatory Keratinised/para
keratinised stratified squamous
Support the stress like compressive and shear forces of mastication and abrasion
Attached gingiva, hard palate and tongue dorsum (rigid mucosa)
because of hard and sharpfood
Specialised Keratinised/
non- keratinised stratified squamous
Unique feature: lingual papillae (tastebuds) have a sensory role, while some have a mechanical
Tongue dorsum
purpose
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7.3 Oral Epithelium: General Features
The oral epithelium forms the outermost or superficial cover of the oral mucosa lining the oral cavity. It is the principal physical barrier shielding the oral tissues from the external environment. The oral epithelium is stratified squamous epithelium: stratified because the cells are arranged in different layers or strata, and squamous because the predominant cells present in the oral epithe­lium are squamous in shape resembling fish’s scales. As mentioned above, the oral mucosa is his­tologically categorised into three types based on their functional requirements of specific areas: masticatory (keratinised) mucosa found on hard palate and gingiva, lining (non- keratinised) on buccal, labial and alveolar mucosa, and specialised (keratinised and non- keratinised) mucosa (tongue dorsum). The keratinised epithelium comprises four layers: stratum basale, stratum spino­sum, stratum granulosum and stratum corneum. In the non- keratinised epithelium, the two deep layers (stratum basale and stratum spinosum) remain the same, but the outer layers are termed the intermediate and superficial layers (Figure7.2). Keratinisation or cornification is a process of cyto­differentiation which the keratinocytes or corneocytes (cells capable of producing a protein called keratin) undergo when proceeding from their post- germinative state (stratum basale) to finally differentiated cells filled with keratin- containing surface layers such as stratum corneum(3). Cells rising from the mitosis in the stratum basale undergo maturation and are displaced towards the surface. Keratinised oral epithelium comprises keratins 1, 6, 10 and 16, while non- keratinised epithelium has keratins 4, 13 and 19(1).
7.4 Stratified Squamous Epithelium
7.4.1 Keratinised Epithelium
All the areas covered by the oral mucosa have stratified squamous epithelium, but the differentia­tion pattern is varied(4). The gingiva and hard palate are covered by keratinised epithelium. In contrast, the floor of the mouth, buccal mucosa and ventral surface of the tongue are covered by a non- keratinised epithelial layer. The specialised oral mucosa is present on the dorsum of the tongue. It is a combination of keratinised and non- keratinised epithelia along with the presence of special structures like papillae(5). Oral keratinised epithelium comprises four layers or strata: stratum basale, stratum spinosum, stratum granulosum and stratum corneum. In about 92% of the population, the keratinised epithelium in the oral cavity is para- keratinised, while the remaining 8% shows ortho- keratinised oral epithelium (1). The para- keratinised epithelial layer contains elongated and pyknotic cell nuclei (irreversible chromatin condensation in the nucleus) with inconspicuous stratum granulosum. In contrast, ortho- keratinised epithelium contains a superficial keratin layer with no evidence of nuclei but a prominent granular cell layer (Figures7.2a,b and7.3).
7.4.1.1 Stratum Basale
Stratum basale is the progenitor cell layer. It comprises a single layer of cuboidal/high cuboidal/ columnar cells attached to the basal lamina (basement membrane) (Figures7.2 and7.3). The attachment takes place with the help of hemidesmosomes. The nuclei of the basal cells are round to ovoid and positioned away from the basal lamina (polarised appearance).
The basal cell population is also divided into two types: serrated and non- serrated basal cells.
In the serrated basal cell layer, cytoplasmic processes, or pedicles (rich in hemidesmosomes) project into underlying connective tissue and create serrations. Thus, the serrated basal cells
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Keratinised
layer
Granular
layer
Prickle cell
layer
Basal cell
layer
(a) (b)
7.4 Stratified Squamous Epithelium
85
Superficial
layer
Intermediate layer
Prickle cell
layer
Basal cell
layer
(c)
Figure7.2 Main types of maturation in human oral epithelium. (a) Ortho- keratin in the gingiva shows a
narrow, darkly staining granular layer. (b) Para- keratinisation in gingiva shows keratin squames that haveretained pyknotic nuclei and a granular layer that contains only a few scattered granules. (c)Non- keratinisation in buccal mucosa shows no clear distinction between cell strata, and nuclei are apparent in the surface layers. Note the difference in thickness, epithelial ridge pattern and maturation patterns. Source:With permission of Pocket Dentistry.
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(a) (b)
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Keratinised surface layer
Granular intermediate layer
Prickle cell layer
Basal layer
Figure7.3 Principal structural features of epithelial cells in successive layers. (a) Ortho- keratinised oral
epithelium. (b) Non- keratinised oral epithelium. Source: Adapted from Squier etal.(6).
anchor the epithelial cells to the underlying connective tissue. Non- serrated cells are stem cells. The stem cells are called slow- cycling cells, and their direct progeny is called the transit- amplifying cells (daughter cells). Stem cells undergo 1– 5 cell divisions to form transit- amplifying cells. These next progeny cells migrate laterally and towards the surface, constituting a clone of differentiating cells. These next progeny cells migrate laterally and towards the surface, constituting a clone of differentiating cells. Cells are pushed towards the surface by pressure generated in the underlying proliferation compartment.
Epithelial projections that penetrate the lamina propria of the oral mucosa are known as rete ridges or epithelial ridges. The bottom of the epithelial ridges has a progenitor compartment at two functionally distant subpopulations of cells. One population represents the cells which produce daughter cells and preserve the proliferating potential. The other largest part is constituted by amplifier cells, which undergo subsequent maturation(1). Basal cells along the base of rete ridges contain few cytoplasmic organelles and are the least differentiated cells. They have a high nuclear– cytoplasmic (N:C) ratio. The pattern generation of the oral epithelial cells is the internal function of the epithelium and is not dependent on the underlying connective tissue. Therefore, connective tissue has no role to play in the formation of basal cells(7).
The proliferation and differentiation of oral epithelial cells are controlled by multiple factors, namely autocrine and paracrine factors by keratinocytes, cell- to- cell nutrient transfer, cytokines, growth factors from connective tissue and systemic factors(8, 9).
Kerato­hyaline granules
Glycogen
Membrane-
coating
granules
Tonobrils
Tonofilaments
Surface layer
Intermediate layer
Prickle cell layer
Basal
layer
7.4.1.2 Stratum Spinosum (Prickle Cell Layer)
Stratum spinosum is the first tier of the differentiation compartment. It comprises numerous larger elliptical/spherical (polygonal) cells known as squamous cells arranged in rows (Figures 7.2 and 7.3). The cells in this layer shrink away from each other during routine tissueprocessing and remain in contact with each other only at the points of intercellular
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bridges/desmosomes ( junctions involved in intercellular adhesion of epithelial cells), hence the name spinous/prickle cells. Thestratum basale and stratum spinosum jointly comprise half to two- thirds of the epithelial thickness from the basement membrane. One of the properties of the oral epithelium is cohesiveness, which forms a strong physical barrier. To facilitate this function, desmosomes and adherens junctions (AJs) for attachment of actin microfilaments and gap junctions develop(1, 7). The AJ provides important adhesive contacts between neighbouring epithelial cells. Gap junctions are intercellular passageways between the membranes of adjacent cells. They facilitate the movement of small molecules and ions between the cells. Rarely, tight/ occluding junctions are evident in the oral epithelium. Tight junctions are multiprotein complexes that seal epithelial cells and prevent leakage of solutes and water(1, 7).
7.4.1.3 Stratum Granulosum
Stratum granulosum consists of large eosinophilic flattened cells without nuclei called squames. They only contain small basophilic granules called keratohyalin granules (Figures7.2 and 7.3). This type of keratinised epithelium is called ortho- keratinised epithelium and is rarely seen in the oral cavity but is common in the cutaneous epithelium. As mentioned earlier, most of the population has para- keratinised epithelium covering the masticatory mucosa. The para- keratinised epithelium has a superficial keratin layer with shrunken or pyknotic nuclei retained. The underlying stratum granulosum has a few keratohyalin granules; thus, it is inconspicuous in the para- keratinised epithelium(1).
7.4.1.4 Stratum Corneum
The stratum corneum is the superficial layer and is called the stratum corneum or the keratinised/ cornified/horny layer (Figures7.2 and7.3). The layer contains keratin.
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7.4.2 Non- keratinised Epithelium
Non- keratinising epithelium covers the lining of mucosa. The stratum basale and spinosum are similar to the keratinised epithelium. However, the desmosomes/prickles are less conspicuous. The morphology of cells above the stratum spinosum remains relatively unchanged. The outer half of the tissue is separated into two zones: the intermediate zone (stratum intermedium) and the superficial zone (stratum superficiale). Stratum granulosum is absent, and the cells of the superfi­cial layer have plump nuclei and are stained pale pink in haematoxylin and eosin (H&E)- stained sections (Figures7.2 and7.3).
7.5 Other Structural Features ofSignificance
7.5.1 Keratin andKeratinocytes
The cornified cell envelope in the keratinised epithelium involves keratins inserted in proteins and enclosed by lipids. The cells generate keratohyaline granules (Figure7.3). The granules discharge intermediate filament protein, which aggregates and causes the collapsing and flattering of keratinocytes called corneocytes. At the same time, other proteins like involucrum, trichohyaline and small proline- rich proteins are produced. Involucrin is a highly reactive, soluble, transglutami­nase substrate protein present in keratinocytes in stratified squamous epithelia(10). Trichohyaline is a structural protein expressed by keratinocytes and functions as a protective barrier.
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7.5.2 Membrane- Coating Granules (MCGs)
MCGs are also known as Odland bodies, keratinosomes and lamellar bodies found in the stratum spinosum and granulosum of the epithelium (Figure7.3). These structures are secreted from keratinocytes, forming an impermeable, lipid- containing membrane that serves as a water barrier for the oral mucosa(11).
7.5.3 Adherens Junctions
AJs are protein complexes present at cell– cell junctions and cell– matrix junctions in epithelium. They resemble bands encircling the cell (zonula adherens) or as attachment spots to the extracel­lular matrix (focal adhesion). The junctions recruit cell– cell contacts and mediate the cell contact’s maturation and maintenance. They are associated with actin cytoskeleton executing functions like initiating and stabilising cell– cell adhesion, regulating actin cytoskeleton, intracellular signalling and transcriptional regulation(12, 13).
7.5.4 Tight Junctions
Tight junctions are intercellular adhesion complexes in the oral epithelium limiting the epithelial permeability. These junctions block the molecules and ions passing through the intercellular spaces. They form a protein network on cellular surfaces. The essential transmembrane proteins found are claudins(13).
7.5.5 Gap Junctions
Gap junctions help in the diffusion of smaller molecules and ions between adjacent cells. They are crucial for electrical transduction, signalling and nutrition(14).
7.5.6 Desmosomes
Desmosomes connect two adjacent cells together and are adherent points forming a continuum of cells by linking integral membrane proteins (Figure7.4). Desmosomes comprise transmembrane glycoproteins called cadherins (desmoglein and desmocollins)(15, 16).
7.5.7 Hemidesmosomes
Hemidesmosomes connect the epithelial basal cells via intermediate filaments to the underlying basal lamina. The transmembrane proteins present are integrin.
7.5.8 Tonofilaments andTonofibrils
Tonofilaments are structural proteins, i.e. intermediate filaments forming tonofibrils. Tonofibrils are fine fibrils that provide a supporting framework for the cells (Figure7.4)(16).
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Desmosom
Tonofibril
e
Figure7.4 Tonofilaments and tonofibrils. Source: Nanci (2008) / with permission of ELSEVIER.
7.6 Non- keratinocytes inthe Oral Epithelium
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The normal oral epithelium also contains a non- keratinising cell population. These include melanocytes, Langerhans (LCs), inflammatory and Merkel cells (MCs).
7.6.1 Melanocytes
Melanocytes are present in the stratum basalis of the oral mucosa and originate from neural crest cells. They get inserted into the epithelium at 11weeks of gestation. The cells’ primary function is to produce melanin pigment, which is responsible for the colour of the mucosa along with haemo­globin and carotenoids. They are a self- reproducing population and possess dendritic processes extending amid keratinocytes(1). Histologically, they can only be identified using special stains for melanin or ‘markers’ for melanocytes (e.g. S- 100). The number of melanocytes in the oral epithe­lium is constant for all individuals. The ratio of melanocytes to keratinocytes ranges from 1:10 to 1:15(17). The diverse skin complexion and colour depend on the size and number of the melanosomes (granules containing melanin) and the form of melanin. Melanin shields the tissues from the harmful consequences of ultraviolet light, reactive oxygen species and free radicals. Physiologically, the number of oral melanocytes increases with age, leading to an amplified amount and intensity of pigmentation(18). Augmented pigmentation of the epithelium may result from inflammatory disorders, medications, recurrent minor injuries, tobacco smoke(19), hormonal disturbances and genetic abnormalities. Melanocytes release melanin into melanosomes and are then transferred by the dendritic processes to the keratinocytes’ cytoplasm. In heavy melanin pigmentation, macrophages are evident in the connective tissue that has taken up melanosomes and are labelled melanophages. Melanin pigmentation is usually seen in the gingiva, buccal mucosa, hard palate and tongue. There is a direct association between melanin pigmentation in the skin and the oral mucosa.
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7.6.2 Langerhans Cells
LCs are dendritic cells seen as small rod/flask- shaped or ‘tennis rackets’- shaped Birbeck granules. They are diffusely scattered within the mucosal epithelium, mostly above the basal cell zone. LCsemerge in the oral mucosa at the same time as, or just before, the melanocytes and undergo limited division. Unlike melanocytes, they travel intra- and extra- epithelial areas and originate from bone marrow(1). LCs are present in clusters around connective tissue papillae in numbers equal to those in the skin. The number of LCs in the mouth is reported to vary inversely with the degree of keratinisation(7).
LCs are imperative in immune surveillance as they are antigen- presenting cells (APCs). They migrate to the lamina propria, reaching the specific lymph nodes. They convert the antigens, i.e. proteins, into peptides and are subsequently presented to T lymphocytes. The marker which can be used to recognise LCs is S- 100(2).
7.6.3 Merkel Cells
MCs are rounded, non- dendritic cells present mainly in the basal third of the oral epithelium. MCsare of endocrine origin arising from the differentiation of an epidermal progenitor and are described as ‘helle Zellen’ (clear cells). They are allied to the nerve fibres in the stratum basale. Merkel considered them having a sensory touch role and called them ‘Tastzellen’ (touch cells). Electron micrographs demonstrate MCs as small, electron- dense endocrine- like granules com­prising intermediate filaments and sometimes desmosomes. In the oral mucosa, MCs are typi­cally positioned in the masticatory mucosa (maxillary and mandibular gingivae and hard palate), but MC– neurite complexes are more in lingual gingivae. Thus, they are slow adapting mechanoreceptors and perform somatosensory communication related to the position of the tongue(20).
7.6.4 Inflammatory Cells
Normally, many inflammatory cells are seen in oral mucous membrane are short lived and not reproduced in the oral mucosa. The most common cell types are the lymphocytes, polymorphonu­clear leukocytes (PMNs) and mast cells. Scattered lymphocytes are frequently observed in the epithelium.
7.7 Self- renewal andTurnover Time ofEpithelia
The oral epithelium sustains its integrity by constant renewal by cell division undergoing mitosis. Oral epithelial replenishment is necessary for keeping the oral mucosa healthy and functional. The oral epithelial cells are regularly replenished by mitotic division in a cyclic manner of around 14– 21days. Epithelial cells from specific sites in the oral cavity have varying epithelial turnover rates. Buccal mucosa has an average of 14days, the floor of the mouth has 20days and the hard palate has 24days of average epithelial turnover rate(21). In wound healing, the epithelial turno­ver rate increases. The turnover time of the epithelial is the time needed to substitute all the cells in the epithelial layer. The turnover period of non- keratinised epithelium is less than that of keratinised epithelium (Table7.2).
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