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Physiological Reviews Jul 2022Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological... (Review)
Review
Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.
Topics: Cell Lineage; Humans; Oral Health; Regeneration; Salivary Glands; Signal Transduction
PubMed: 35343828
DOI: 10.1152/physrev.00015.2021 -
Journal of Oral Rehabilitation Sep 2018Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and... (Review)
Review
Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.
Topics: Humans; Mastication; Oral Health; Saliva; Salivary Glands; Salivation; Xerostomia
PubMed: 29878444
DOI: 10.1111/joor.12664 -
Periodontology 2000 Feb 2016Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands--the submandibular, parotid and sublingual glands--along with secretions from... (Review)
Review
Saliva in the mouth is a biofluid produced mainly by three pairs of major salivary glands--the submandibular, parotid and sublingual glands--along with secretions from many minor submucosal salivary glands. Salivary gland secretion is a nerve-mediated reflex and the volume of saliva secreted is dependent on the intensity and type of taste and on chemosensory, masticatory or tactile stimulation. Long periods of low (resting or unstimulated) flow are broken by short periods of high flow, which is stimulated by taste and mastication. The nerve-mediated salivary reflex is modulated by nerve signals from other centers in the central nervous system, which is most obvious as hyposalivation at times of anxiety. An example of other neurohormonal influences on the salivary reflex is the circadian rhythm, which affects salivary flow and ionic composition. Cholinergic parasympathetic and adrenergic sympathetic autonomic nerves evoke salivary secretion, signaling through muscarinic M3 and adrenoceptors on salivary acinar cells and leading to secretion of fluid and salivary proteins. Saliva gland acinar cells are chloride and sodium secreting, and the isotonic fluid produced is rendered hypotonic by salivary gland duct cells as it flows to the mouth. The major proteins present in saliva are secreted by salivary glands, creating viscoelasticity and enabling the coating of oral surfaces with saliva. Salivary films are essential for maintaining oral health and regulating the oral microbiome. Saliva in the mouth contains a range of validated and potential disease biomarkers derived from epithelial cells, neutrophils, the microbiome, gingival crevicular fluid and serum. For example, cortisol levels are used in the assessment of stress, matrix metalloproteinases-8 and -9 appear to be promising markers of caries and periodontal disease, and a panel of mRNA and proteins has been proposed as a marker of oral squamous cell carcinoma. Understanding the mechanisms by which components enter saliva is an important aspect of validating their use as biomarkers of health and disease.
Topics: Animals; Humans; Saliva; Salivary Glands
PubMed: 26662479
DOI: 10.1111/prd.12116 -
Cells Aug 2019Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the... (Review)
Review
Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the functionality of these glands, greatly impacting the quality of life of patients. To date, no definitive therapeutic approach can compensate the impairment of salivary glands, and treatment are purely symptomatic. Understanding the cellular and molecular control of salivary glands function is, therefore, highly relevant for therapeutic purposes. In this review, we provide a starting platform for future studies in basic biology and clinical research, reporting classical ideas on salivary gland physiology and recently developed technology to guide regeneration, reconstruction and substitution of the functional organs.
Topics: Animals; Female; Gene Regulatory Networks; Humans; Male; Mice; Regeneration; Salivary Glands; Sex Characteristics; Species Specificity
PubMed: 31455013
DOI: 10.3390/cells8090976 -
Nature Reviews. Rheumatology Jun 2021In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the... (Review)
Review
In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-κB pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4 T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS.
Topics: B-Lymphocytes; CD4-Positive T-Lymphocytes; Epithelial Cells; Humans; Immune Checkpoint Inhibitors; Inflammasomes; Interferons; Lymphoma, B-Cell, Marginal Zone; NF-kappa B; Salivary Glands; Sjogren's Syndrome
PubMed: 33911236
DOI: 10.1038/s41584-021-00605-2 -
Drugs in R&D Mar 2017Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality... (Review)
Review
A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.
BACKGROUND
Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist.
OBJECTIVE
Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea.
DATA SOURCES
Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices.
LIMITATIONS
While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search.
CONCLUSIONS
We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Oral Medicine; Salivary Glands; Sialorrhea; Xerostomia
PubMed: 27853957
DOI: 10.1007/s40268-016-0153-9 -
Cell Jul 2021Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of...
Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in the embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required β1-integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells.
Topics: Animals; Basement Membrane; Cell Adhesion; Cell Division; Cell Movement; Cell Tracking; Cell-Matrix Junctions; Embryo, Mammalian; Epithelial Cells; Epithelium; Gene Expression Regulation, Developmental; HEK293 Cells; Humans; Integrins; Mice; Models, Biological; Morphogenesis; Salivary Glands; Transcriptome
PubMed: 34133940
DOI: 10.1016/j.cell.2021.05.015 -
Oral and Maxillofacial Surgery Clinics... Aug 2021Although a rare sequala of soft tissue injury, salivary gland trauma may result in significant morbidity. Salivary gland injury can involve the major as well as the... (Review)
Review
Although a rare sequala of soft tissue injury, salivary gland trauma may result in significant morbidity. Salivary gland injury can involve the major as well as the minor glands. Because of the proximity of adjacent vital structures, a thorough history and physical examination are mandatory during patient evaluation. Trauma to the major salivary glands may involve the parenchyma, duct, or neural injury. Treatment requires adherence to primary principles of soft tissue management. Ductal and neural injury should be repaired primarily. Sialocele and fistula are potential complications of repaired and unrepaired salivary gland injury.
Topics: Humans; Parotid Gland; Salivary Gland Diseases; Salivary Glands
PubMed: 34116909
DOI: 10.1016/j.coms.2021.04.008 -
European Journal of Pharmaceutics and... Sep 2019Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of... (Review)
Review
Saliva is a multifaceted bodily fluid that is often taken for granted but is indispensable for oral health and overall well-being in humans. Although mainly comprised of water (99.5%), proteins, ions and enzymes turn saliva into a viscoelastic solution that performs a variety of vital tasks. This review article gives a brief overview of the salivary gland system, as well as the composition, output and functions of saliva. It also addresses the current applications of saliva for diagnostic purposes, the clinical relevance of saliva in oral diseases as well as current treatment options.
Topics: Body Fluids; Humans; Mouth Diseases; Oral Health; Saliva; Salivary Glands
PubMed: 31220573
DOI: 10.1016/j.ejpb.2019.06.016 -
Advances in Oto-rhino-laryngology 2016The malignant or benign nature of a salivary gland (SG) tumor can be predicted with reasonably high accuracy by imaging. There is some overlap between the imaging... (Review)
Review
The malignant or benign nature of a salivary gland (SG) tumor can be predicted with reasonably high accuracy by imaging. There is some overlap between the imaging findings of benign and malignant tumors, particularly for low-grade malignancies, and tissue diagnosis remains necessary for definitive diagnosis. Magnetic resonance imaging is the modality of choice for the evaluation of salivary neoplasms, as it allows for delineation of local infiltration, perineural spread and intracranial extension. This review will focus on the advanced imaging techniques that help to characterize SG tumors. A brief overview of the conventional imaging features of SG neoplasms is necessary before a discussion of the advanced imaging methods.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Salivary Gland Neoplasms; Salivary Glands
PubMed: 27093072
DOI: 10.1159/000442122