Critical Reviews in Oral Biology & Medicine

The Official Publication of the American Association of Oral Biologists

A Publication of the International/American Associations for Dental Research
Table of Contents for Volume 2, 1991

Volume 2, Issue 1
Volume 2, Issue 2
Volume 2, Issue 3
Volume 2, Issue 4

Volume 2, Issue 1

• Cutler LS; Gremski W
• Administration & Research, University of Connecticut Health Center, Farmington 06030.
• Pages 1-12.

The full expression of both morphogenesis and secretory cell differentiation in salivary glands is modulated or controlled, at least in part, by interactions between the salivary epithelium and the surrounding mesenchyme. Salivary gland morphogenesis and cytodifferentiation are partially linked but independently regulated processes. This presentation reviews the information that establishes the role of various extracellular matrix molecules and direct epithelial-mesenchymal interactions in the induction, control, and maintenance of morphogenesis and secretory cell differentiation in salivary glands.

• Squier CA
• Dows Institute for Dental Research, University of Iowa, College of Dentistry, Iowa City 52242.
• Pages 13-32.

In discussing permeability, we are describing one of the fundamental barrier functions of oral mucosa. Despite assumptions to the contrary, the oral mucosa is not a uniformly, highly permeable tissue like gut, but shows regional variation. The keratinized areas, such as gingiva and hard palate, are least permeable and nonkeratinized lining areas are most permeable. This variation appears to reflect differences in the types of lipid making up the intercellular permeability barrier in the superficial layers of the epithelium. Differences in permeability may be related to regional differences in the prevalence of certain mucosal diseases and can be utilized to advantage for local and systemic drug delivery.

• Lund JP
• Department de Stomatologie, Universite de Montreal, Canada.
• Pages 33-64.

This review describes the patterns of mandibular movements that make up the whole sequence from ingestion to swallowing food, including the basic types of cycles and their phases. The roles of epithelial, periodontal, articular, and muscular receptors in the control of the movements are discussed. This is followed by a summary of our knowledge of the brain stem neurons that generate the basic pattern of mastication. It is suggested that the production of the rhythm, and of the opener and closer motoneuron bursts, are independent processes that are carried out by different groups of cells. After commenting on the relevant properties of the trigeminal and hypoglossal motoneurons, and of internuerons on the cortico-bulbar and reflex pathways, the way in which the pattern generating neurons modify sensory feedback is discussed.

• Schenkein HA
• Clinical Research Center for Periodontal Diseases, Virginia Commonwealth University, Richmond 23298.
• Pages 65-81.

The complement system has been implicated as both a pathogenic mechanism and a means of protection in periodontal diseases. It is well known that bacteria activate complement; such activation can initiate a number of events, including bacterial opsonization and killing, release of inflammatory agents, and modulation of other immune reactions. Cleavage of complement proteins has been observed in gingival fluids from individuals with periodontal disease and some investigators have observed complement deposition in diseased gingival tissues. Furthermore, a number of bacterial from individuals with periodontal diseases have been found to activate complement in vitro; some of these organisms appear to have the capacity to evade opsonization due to their proteolytic capacity. However, concrete evidence is not yet available that indicates that complement activation occurs in human periodontal disease and is important in either its pathogenesis or in protection against bacterial virulence factors.

• Stanford CM; Keller JC
• Dows Institute for Dental Research, University of Iowa, College of Dentistry, Iowa City 52242.
• Pages 83-101.

Osseointegration has been defined as the direct structural and functional connection between ordered, living bone and the surface of a load-carrying implant. To date, this concept has been described by descriptive histological and ultrastructural criteria but not by biochemical means. This review evaluates the basic science work performed on this concept and then applies the concept to the principle of osseous healing. Specific studies are cited where alterations in the healing response are due to clinical management of implant placement and how studies of surface properties may lead to further insights on implant design and prognosis. In addition, a review of bone expression as a function of in vitro stress applications is given. This is followed by an indepth review of the collagens and noncollagenous proteins, described to date, within isolated bone matrix. It is this collagenous matrix (especially type I) that is described as being close to and oriented with a glycoprotein component next to the implant surface. In turn, the large family of noncollagenous proteins are important in mediating bone proliferation, matrix accumulation, orientation, mineralization, and turnover. This section is followed by a discussion of specific growth factors as they may relate to osseous healing around an implant.

• Hassell TM; Hefti AF
• Department of Periodontology, College of Dentistry, University of Florida, Gainesville 32610.
• Pages 103-37.

Volume 2, Issue 2

• Kousvelari E; Tabak LA
• Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
• Pages 139-151.

The presence of a protein in the cell is the result of a complex pathway that is known by the term gene expression. In this article we review the existing literature on the structure and expression of representative salivary gland genes and their regulated expression during development and upon extracellular stimulation. The expression of one of the "nuclear" protooncogenes, c-fos, in rat parotid glands is also discussed. Finally, we present some suggestions for future studies that will help to understand the mechanisms leading to gene regulation in rat salivary glands.

• Steele C; Shillitoe EJ
• Department of Microbiology, University of Texas Health Science Center, Houston 77225.
• Pages 153-175.

Oral cancer is a disease with a complex etiology. There is evidence for important roles of smoking, drinking, and genetic susceptibility, as well as strong indications that DNA viruses could be involved. The herpes simplex virus type 1 has been associated with oral cancer by serological studies, and animal models and in vitro systems have demonstrated that it is capable of inducing oral cancer. Papillomaviruses are found in many oral cancers and are also capable of transforming cells to a malignant phenotype. However, both virus groups depend on co-factors for their carcinogenic effects. Future research on viruses and oral cancer is expected to clarify the role of these viruses, and this will lead to improvements in diagnosis and treatment of the disease.

• Holt SC; Bramanti TE
• Department of Periodontics, University of Texas Health Science Center, San Antonio 78284-7894.
• Pages 177-281

The classic progression of the development of periodontitis with its associated formation of an inflammatory lesion is characterized by a highly reproducible microbiological progression of a Gram-positive microbiota to a highly pathogenic Gram-negative one. While this Gram-negative microbiota is estimated to consist of at least 300 different microbial species, it appears to consist of a very limited number of microbial species that are involved in the destruction of periodontal diseases. Among these "putative periodontopathic species" are members of the genera Porphyromonas, Bacteroides, Fusobacterium, Wolinella, Actinobacillus, Capnocytophaga, and Eikenella. While members of the genera Actinomyces and Streptococcus may not be directly involved in the microbial progression, these species do appear to be essential to the construction of the network of microbial species that comprise both the subgingival plaque matrix. The temporal fluctuation (emergence/disappearance) of members of this microbiota from the developing lesion appears to depend upon the physical interaction of the periodontal pocket inhabitants, as well as the utilization of the metabolic end-products of the respective species intimately involved in the disease progression. A concerted action of the end-products of prokaryotic metabolism and the destruction of host tissues through the action of a large number of excreted proteolytic enzymes from several of these periodontopathogens contribute directly to the periodontal disease process.

Volume 2, Issue 3

• ten Cate JM; Featherstone JD
• Department of Cariology and Endodontology, Academic Centre for Dentistry, Amsterdam, The Netherlands.
• Pages 283-296.

For many years after the discovery of its caries preventive effect, fluoride was thought to be primarily active by lowering the solubility of the apatitic mineral phase of the dental hard tissues. Recent findings have shed new light on the mechanisms by which fluoride inhibits or delays dental caries. Fluoride present in the oral fluids alters the rate of the naturally occurring dissolution and reprecipitation processes at the tooth-oral fluid interface. Demineralization of enamel is inhibited by concentrations of fluoride in the sub-ppm range. Likewise, remineralization of incipient caries lesions (the earliest stage of enamel caries) is accelerated by trace amounts of fluoride. As these two processes comprise dental caries the physiological balance between hard tissue breakdown and repair is favorably shifted by fluoride. The driving force for both phenomena is thermodynamic, that is, fluorapatite or a fluoridated hydroxyapatite may form when fluoride is supplied at low concentrations. This article critically reviews the current information about tooth-fluoride interactions, both from laboratory and clinical studies.

• Golub LM; Ramamurthy NS; McNamara TF; Greenwald RA; Rifkin BR
• Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York, Stony Brook.
• Pages 297-321.

Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity. The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut. Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed.

• Uitto VJ; Larjava H
• University of British Columbia, Faculty of Dentistry, Department of Oral Biology, Vancouver, Canada.
• Pages 323-354

Knowledge of extracellular matrix molecules and their cell receptors has increased exponentially during the last 2 decades. It is now known that the structure and function of each tissue is based on specific combinations of matrix molecules. The major constituents of the extracellular matrix are collagens, proteoglycans, and adhesive glycoproteins. The rapid development of biochemical, molecular biological, and immunological research has revealed a lot of interesting details pertaining to these molecules. Several new collagen types have been discovered. In addition to being responsible for the strength and form of tissues, each collagen type has specific sequences providing them with special features such as flexibility and the ability to interact with other matrix molecules and cells. Proteoglycans are another large group of matrix molecules with a variety of functions. Proteoglycans play an important role in tissue resilience and filtering. Some proteoglycans have a capacity to specifically bind other matrix molecules and growth factors, while others act as matrix receptors on the cell surface. An important part of regulation of the cell behavior is played by adhesive glycoproteins belonging to the fibronectin and laminin families. Several isoforms of fibronectin and laminin that result from alternative RNA splicing serve specific functions such as controlling the attachment, migration, and synthetic activity of cells. A major group of cell receptors for cell-matrix and cell-cell interactions is termed integrins. The integrins are cell surface proteins composed of two polypeptides whose structure dictates the specificity of each receptor. The cytoplasmic domain of the integrins interacts with cytoskeletal elements within the cell, and thereby relays the information from the extracellular space into the protein synthesis machinery. The expression of the integrins is controlled by the extracellular matrix and growth factors, most notably TGF beta. During periodontal diseases several aspects of the cell-matrix interactions may be disturbed. Therefore, an understanding of the special features of the extracellular matrix and their receptors in periodontal tissues is a prerequisite for developing new approaches to the prevention and treatment of periodontal diseases.

• Boackle RJ
• Department of Microbiology and Immunology, College of Dental Medicine, Medical University of South Carolina, Charleston.
• Pages 355-367.

When complement first contacts salivary secretions, as when gingival crevicular fluid first meets saliva at the gingival margin, complement function is enhanced. The immediate potentiation of the complement system at equal volume ratios of serum to saliva is due to several factors, including the lower ionic strength of saliva when compared with serum and the presence of certain salivary glyproteins such as the nonimmunoglobulin agglutinins that appear to simultaneously activate C1 and affect (sequester) certain complement control proteins, such as Factor H. This initial potentiation of the complement cascade by saliva may aid in defending the area immediately above the gingival crevice from oral microbiota that are being coated with a combination of serous exudate components and salivary components. As serum becomes much more diluted with saliva (i.e., crevicular fluid moves away from the supragingival area), the acidic proline-rich salivary proteins (APRP) begin to disrupt the unbound C1q-C1r2-C1s2 macromolecular complexes. Thus, the APRP along with other C1 fixing substances in saliva appear to restrict complement function, but only when the ratios of saliva to serum exceed 250:1. Since certain salivary glycoproteins bind to viruses, the potentiation of the complement system by saliva may also play a role in neutralizing certain viral infections on mucosal surfaces where tissue transudates containing complement begin to contact mucosal secretions such as saliva. Again, the ratio of serous fluid to mucosal secretion appears to be an important factor. This article also discusses some of our preliminary data and speculations concerning the binding of the self-associating high-molecular-weight nonimmunoglobulin salivary agglutinins (NIA) with the envelope of the human immunodeficiency virus (HIV) and the possible cooperative role of C1q and fibronectin in aiding neutralization of HIV infectivity.

• Boskey AL
• Laboratory for Ultrastructural Biochemistry, Hospital for Special Surgery, New York, New York.
• Pages 369-387.

The extracellular matrix of dentin consists of mineral (hydroxyapatite), collagen, and several noncollagenous matrix proteins. These noncollagenous matrix proteins may be mediators of cell-matrix interactions, matrix maturation, and mineralization. This review describes the current knowledge of the chemistry of mineral crystal formation in dentin with special emphasis on the roles of the dentin matrix proteins. The functions of some of these matrix proteins in the mineralization process have been deduced based on in vitro studies. Functions for others have been postulated based on analogy with some of the bone matrix proteins. Evidence suggests that several of these matrix proteins may have multiple effects on nucleation, crystal growth, and orientation of dentin hydroxyapatite.

• Roodman GD
• Department of Medicine, University of Texas Health Science Center, San Antonio.
• Pages 389-409.

The osteoclast is the primary bone resorbing cell. It is a highly specialized multinucleated cell whose primary function is to help in the control of calcium homeostasis. The osteoclast has been very difficult to study because of its relative inaccessability, low numbers, and fragility when isolated from bone. Recently, techniques have been developed to study the cell biology of the osteoclast that have expanded our ability to understand the biological and functional properties of osteoclasts. In this article, studies on the origin of the osteoclast are reviewed and the differentiation markers that are used to detect cells in the osteoclast lineage are discussed. Factors that affect osteoclast differentiation are presented and model systems currently in use for studying osteoclast differentiation are evaluated for their relative strengths and weaknesses. In addition, osteoclast differentiation during tooth eruption and root resorption and the effects of bone matrix elements on osteoclast differentiation are reviewed.

Volume 2, Issue 4

• Davidovitch Z
• Department of Orthodontics, Ohio State University College of Dentistry, Columbus.
• Pages 411-450.

This article reviews the evolution of concepts regarding the biological foundation of force-induced tooth movement. Nineteenth century hypotheses proposed two mechanisms: application of pressure and tension to the periodontal ligament (PDL), and bending of the alveolar bone. Histologic investigations in the early and middle years of the 20th century revealed that both phenomena actually occur concomitantly, and that cells, as well as extracellular components of the PDL and alveolar bone, participate in the response to applied mechanical forces, which ultimately results in remodeling activities. Experiments with isolated cells in culture demonstrated that shape distortion might lead to cellular activation, either by opening plasma membrane ion channels, or by crystallizing cytoskeletal filaments. Mechanical distortion of collagenous matrices, mineralized or non-mineralized, may, on the other hand, evoke the development of bioelectric phenomena (stress-generated potentials and streaming potentials) that are capable of stimulating cells by altering the electric charge on their membrane or their fluid envelope. In intact animals, mechanical perturbations on the order of about 1 min/d are apparently sufficient to cause profound osteogenic responses, perhaps due to matrix proteoglycan-related "strain memory". Enzymatically isolated human PDL cells respond biochemically to mechanical and chemical signals. The latter include endocrines, autocrines, and paracrines. Histochemical and immunohistochemical studies showed that during the early places of tooth movement, PDL fluids are shifted, and cells and matrix are distorted. Vasoactive neurotransmitters are released from periodontal nerve terminals, causing leukocytes to migrate out of adjacent capillaries. Cytokines and growth factors are secreted by these cells, stimulating PDL cells and alveolar bone lining cells to remodel their related matrices. This remodeling activity facilitates movement of teeth into areas in which bone had been resorbed. This emerging information suggests that in the living mammal, many cell types are involved in the biological response to applied mechanical stress to teeth, and thereby to bone. Essentially, cells of the nervous, immune, and endocrine systems become involved in the activation and response of PDL and alveolar bone cells to applied stresses. This fact implies that research in the area of the biological response to force application to teeth should be sufficiently broad to include explorations of possible associations between physical, cellular, and molecular phenomena. The goals of this investigative field should continue to expound on fundamental principles, particularly on extrapolating new findings to the clinical environment, where millions of patients are subjected annually to applications of mechanical forces to their teeth for long periods of time in an effort to improve their position in the oral cavity.

• Milam SB; Haskin C; Zardeneta G; Chen D; Magnuson VL; Klebe RJ; Steffenson B
• Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
• Pages 451-491.

• Dabelsteen E; Mandel U; Clausen H
• Royal Dental College, Copenhagen, Denmark.
• Pages 493-507.

Carbohydrates of the epithelial cell membrane are involved in cell-cell and cell-substrate interaction, and changes are seen in relationship to cell differentiation and neoplastic transformation. The terminal part of carbohydrate structures carried on oral epithelial cells often expresses antigens of the ABO and Lewis blood group systems. The expression of these antigens are in oral mucosa genetically regulated by the A, B, H, Lewis, and secretor genes with subsequent correspondence between the blood group antigens expressed on erythrocytes and on oral epithelial cells. Variation in expression of carbohydrates is also seen in relationship to terminal differentiation in that blood group antigens and their immediate precursor structures are sequentially expressed on cells during their pathway through the epithelium. Various organs and tissues differ in their expression of cell surface carbohydrates. In oral mucosa, a close relationship is seen between the type of tissue differentiation and expression of blood group antigen; keratinized, nonkeratinized, and junctional epithelium all show different patterns of carbohydrate expression.