Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists最新文献

The past 50 years of research on the mechanical properties of human dentin are reviewed. Since the body of work in this field is highly inconsistent, it was often necessary to re-analyze prior studies, when possible, and to re-assess them within the framework of composite mechanics and dentin structure. A critical re-evaluation of the literature indicates that the magnitudes of the elastic constants of dentin must be revised considerably upward. The Young's and shear moduli lie between 20-25 GPa and 7-10 GPa, respectively. Viscoelastic behavior (time-dependent stress relaxation) measurably reduces these values at strain rates of physiological relevance; the reduced modulus (infinite relaxation time) is about 12 GPa. Furthermore, it appears as if the elastic properties are anisotropic (not the same in all directions); sonic methods detect hexagonal anisotropy, although its magnitude appears to be small. Strength data are re-interpreted within the framework of the Weibull distribution function. The large coefficients of variation cited in all strength studies can then be understood in terms of a distribution of flaws within the dentin specimens. The apparent size-effect in the tensile and shear strength data has its origins in this flaw distribution, and can be quantified by the Weibull analysis. Finally, the relatively few fracture mechanics and fatigue studies are discussed. Dentin has a fatigue limit. For stresses smaller than the normal stresses of mastication, approximately 30 MPa, a flaw-free dentin specimen apparently will not fail. However, a more conservative approach based on fatigue crack growth rates indicates that if there is a pre-existing flaw of sufficient size (approximately 0.3-1.0 mm), it can grow to catastrophic proportion with cyclic loading at stresses below 30 MPa.

The location of the primary tumor or lymph node metastases dictates the inclusion of the oral cavity, salivary glands, and jaws in the radiation treatment portals for patients who have head and neck cancer. The clinical sequelae of the radiation treatment include mucositis, hyposalivation, loss of taste, osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose-limiting and have a tremendous effect on the patient's quality of life. Most treatment protocols to prevent these sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. Many of these alternatives either need further study before they can be incorporated into the protocols commonly used to prevent and treat the radiation-related oral sequelae or await implementation of these protocols. In this review, the various possibilities for prevention and/or treatment of radiation-induced changes in healthy oral tissues and their consequences are discussed.

The scientific literature during the last ten years has seen an exponential increase in the number of reports claiming links for genetic polymorphisms with a variety of medical diseases, particularly chronic immune and inflammatory conditions. Recently, periodontal research has contributed to this growth area. This new research has coincided with an increased understanding of the genome which, in turn, has permitted the functional interrelationships of gene products with each other and with environmental agents to be understood. As a result of this knowledge explosion, it is evident that there is a genetic basis for most diseases, including periodontitis. This realization has fostered the idea that if we can understand the genetic basis of diseases, genetic tests to assess disease risk and to develop etiology-based treatments will soon be reality. Consequently, there has been great interest in identifying allelic variants of genes that can be used to assess disease risk for periodontal diseases. Reports of genetic polymorphisms associated with periodontal disease are increasing, but the limitations of such studies are not widely appreciated. While there have been dramatic successes in the identification of mutations responsible for rare genetic conditions, few genetic polymorphisms reported for complex genetic diseases have been demonstrated to be clinically valid, and fewer have been shown to have clinical utility. Although geneticists warn clinicians on the over-enthusiastic use and interpretation of their studies, there continues to be a disparity between the geneticists and the clinicians in the emphasis placed on genes and genetic polymorphism associations. This review critically reviews genetic associations claimed for periodontal disease. It reveals that, despite major advances in the awareness of genetic risk factors for periodontal disease (with the exception of periodontitis associated with certain monogenetic conditions), we are still some way from determining the genetic basis of both aggressive and chronic periodontitis. We have, however, gained considerable insight into the hereditary pattern for aggressive periodontitis. Related to our understanding that it is autosomal-dominant with reduced penetrance comes a major clinically relevant insight into the risk assessment and screening for this disease, in that we appreciate that parents, offspring, and siblings of patients affected with aggressive periodontitis have a 50% risk of this disease also. Nevertheless, we must exercise caution and proper scientific method in the pursuit of clinically valid and useful genetic diagnostic tests for chronic and aggressive periodontitis. We must plan our research using plausible biological arguments and carefully avoid the numerous bias and misinterpretation pitfalls inherent in researching genetic associations with disease.

Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response-in particular, CD4+ T-cells-plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, 'RANK-L', which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

The temporomandibular joint (TMJ) disc consists mainly of collagen fibers and proteoglycans constrained in the interstices of the collagen fiber mesh. This construction results in a viscoelastic response of the disc to loading and enables the disc to play an important role as a stress absorber during function. The viscoelastic properties depend on the direction (tension, compression, and shear) and the type of the applied loading (static and dynamic). The compressive elastic modulus of the disc is smaller than its tensile one because the elasticity of the disc is more dependent on the collagen fibers than on the proteoglycans. When dynamic loading occurs, the disc is likely to behave less stiffly than under static loading because of the difference of fluid flow through and out of the disc during loading. In addition, the mechanical properties change as a result of various intrinsic and extrinsic factors in life such as aging, trauma, and pathology. Information about the viscoelastic behavior of the disc is required for its function to be understood and, for instance, for a suitable TMJ replacement device to be constructed. In this review, the biomechanical behavior of the disc in response to different loading conditions is discussed.

Discrepancies in size and shape of the jaws are the underlying etiology in many orthodontic and orthognathic surgery patients. Genetic factors combined with environmental interactions have been postulated to play a causal or contributory role in these craniofacial abnormalities. Along with the soon-to-be-available complete human and mouse genomic sequence data, mouse mutants have become a valuable tool in the functional mapping of genes involved in the development of human maxillofacial dysmorphologies. We review two powerful methods in such efforts: N-ethyl-N-nitrosourea (ENU) large-scale mutagenesis and quantitative trait linkage (QTL) analysis. The former aims at producing a plethora of novel variants of particular trait(s), and ultimately mapping the point mutations responsible for the appearance of these new traits. In contrast, the latter applies intensive breeding and mapping techniques to identify multiple loci (and, subsequently, genes) contributing to the phenotypic difference between the tested strains. A prerequisite for either approach to studying variations in the traits of interest is the application of effective mouse cephalometric phenotype analysis and rapid DNA mapping techniques. These approaches will produce a wealth of new data on critical genes that influence the size and shape of the human face.

Dental enamel forms as a progressively thickening extracellular layer by the action of proteins secreted by ameloblasts. The most abundant enamel protein is amelogenin, which is expressed primarily from a gene on the X-chromosome (AMELX). The two most abundant non-amelogenin enamel proteins are ameloblastin and enamelin, which are expressed from the AMBN and ENAM genes, respectively. The human AMBN and ENAM genes are located on chromosome 4q13.2. The major secretory products of the human AMELX, AMBN, and ENAM genes have 175, 421, and 1103 amino acids, respectively, and are all post-translationally modified, secreted, and processed by proteases. Mutations in AMELX have been shown to cause X-linked amelogenesis imperfecta (AI), which accounts for 5% of AI cases. Mutations in ENAM cause a severe form of autosomal-dominant smooth hypoplastic AI that represents 1.5%, and a mild form of autosomal-dominant local hypoplastic AI that accounts for 27% of AI cases in Sweden. The discovery of mutations in the ENAM gene in AI kindreds proved that enamelin is critical for proper dental enamel formation and that it plays a role in human disease. Here we review how enamelin was discovered, what is known about enamelin protein structure, post-translational modifications, processing by proteases, and its potentially important functional properties such as its affinity for hydroxyapatite and influence on crystal growth in vitro. The primary structures of human, porcine, mouse, and rat enamelin are compared, and the human enamelin gene, its structure, chromosomal localization, temporal and spatial patterns of expression, and its role in the etiology of amelogenesis imperfecta are discussed.

Dental clinicians are confronted with an increasing number of medically compromised patients who require implant surgery for their oral rehabilitation. However, there are few guidelines on dental implant therapy in this patient category, so that numerous issues regarding pre- and post-operative management remain unclear to the dental clinician. Therefore, the aim of the present review is to offer a critical evaluation of the literature and to provide the clinician with scientifically based data for implant therapy in the medically compromised patient. This review presents the current knowledge regarding the influence of the most common systemic and local diseases on the outcome of dental implant therapy, e.g., abnormalities in bone metabolism, diabetes mellitus, xerostomia, and ectodermal dysplasias. Specific pathophysiologic aspects of the above-mentioned diseases as well as their potential implications for implant success are critically appraised. In line with these implications, guidelines for pre- and post-operative management that may assist in the successful implant-supported rehabilitation of this patient category are proposed.

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.

Present tooth-bleaching techniques are based upon hydrogen peroxide as the active agent. It is applied directly, or produced in a chemical reaction from sodium perborate or carbamide peroxide. More than 90% immediate success has been reported for intracoronal bleaching of non-vital teeth, and in the period of 1-8 years' observation time, from 10 to 40% of the initially successfully treated teeth needed re-treatment. Cervical root resorption is a possible consequence of internal bleaching and is more frequently observed in teeth treated with the thermo-catalytic procedure. When the external tooth-bleaching technique is used, the first subjective change in tooth color may be observed after 2-4 nights of tooth bleaching, and more than 90% satisfactory results have been reported. Tooth sensitivity is a common side-effect of external tooth bleaching observed in 15%-78% of the patients, but clinical studies addressing the risk of other adverse effects are lacking. Direct contact with hydrogen peroxide induced genotoxic effects in bacteria and cultured cells, whereas the effect was reduced or abolished in the presence of metabolizing enzymes. Several tumor-promoting studies, including the hamster cheek pouch model, indicated that hydrogen peroxide might act as a promoter. Multiple exposures of hydrogen peroxide have resulted in localized effects on the gastric mucosa, decreased food consumption, reduced weight gain, and blood chemistry changes in mice and rats. Our risk assessment revealed that a sufficient safety level was not reached in certain clinical situations of external tooth bleaching, such as bleaching one tooth arch with 35% carbamide peroxide, using several applications per day of 22% carbamide peroxide, and bleaching both arches simultaneously with 22% carbamide peroxide. The recommendation is to avoid using concentrations higher than 10% carbamide peroxide when one performs external bleaching. We advocate a selective use of external tooth bleaching based on high ethical standards and professional judgment.