Advances in Dental Research最新文献

This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of supplementation.

New insights into the biological mechanisms involved in modulating periodontal inflammation and alveolar bone loss are paving the way for novel therapeutic strategies for periodontitis. The neutrophil adhesion cascade for transmigration in response to infection or inflammation is a key paradigm in immunity. Developmental endothelial locus-1 (Del-1) is one of several newly identified endogenous inhibitors of the leukocyte adhesion cascade. Del-1 competes with intercellular adhesion molecule-1 (ICAM-1) on endothelial cells for binding to the LFA-1 integrin on neutrophils, thereby regulating neutrophil recruitment and local inflammation. In animal periodontitis models, Del-1 deficiency resulted in severe inflammation and alveolar bone loss, but local treatment with recombinant Del-1 prevented neutrophil infiltration and bone loss. The expression of Del-1 is inhibited by the pro-inflammatory cytokine IL-17. Nucleic-acid-receptor-mediated inflammatory responses may be important in periodontal disease pathogenesis. Bacterial nucleic acids released during inflammation are detected by host microbial DNA sensors, e.g., Toll-like receptor-9 (TLR-9), leading to the activation of pro- and/or anti-inflammatory signaling pathways. DNA from periodontitis-associated bacteria induced pro-inflammatory cytokine production in human macrophage-like cells through the TLR-9 and NF-κB signaling pathways, but had less effect on human osteoblasts. Inhibition of TLR-9 signaling in human macrophages reduced cytokine production in response to P. gingivalis DNA. Differential expression of a polymorphic site in the TLR-9 gene promoter region and increased TLR-9 gene and protein expression were reported in chronic periodontitis. Further research to confirm that periodontal bacterial DNA contributes to destructive inflammation in vivo could provide alternative therapeutic targets to control periodontitis.

Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application.

Intense environmental concerns recently have prompted dentistry to evaluate the performance and environmental impact of existing restoration materials. Doing so entices us to explore the 'what if?' innovation in materials science to create more ideal restorative materials. Articulating a specification for our design and evaluation methods is proving to be more complicated than originally anticipated. Challenges exist not only in specifying how the material should be manipulated and perform clinically but also in understanding and incorporating implications of the skill of the operator placing the restoration, economic considerations, expectations patients have for their investment, cost-effectiveness, influences of the health care system on how and for whom restorations are to be placed, and global challenges that limit the types of materials available in different areas of the world. The quandary is to find ways to actively engage multiple stakeholders to agree on priorities and future actions to focus future directions on the creation of more ideal restorative materials that can be available throughout the world.

Innovations in materials science, both within and outside of dentistry, open opportunities for the development of exciting direct restorative materials. From rich dialog among experts from dental and non-dental academic institutions and industry, as well as those from policy, research funding, and professional organizations, we learned that capitalizing on these opportunities is multifactorial and far from straightforward. Beginning from the point when a restoration is needed, what materials, delivery systems, and skills are needed to best serve the most people throughout the world's widely varied economic and infrastructure systems? New research is a critical element in progress. Effective advocacy can influence funding and drives change in practice and policy. Here we articulate both research and advocacy priorities, with the intention of focusing the energy and expertise of our best scientists on making a difference, bringing new innovations to improve oral health.

During the past 50 years, a series of key UN conferences have established a framework to minimize human health risks from environmental exposures to key chemicals. In January 2013, more than 140 countries agreed to the text of new treaty to minimize Hg effects on the environment (the Minamata Convention). Dental caries is omnipresent around the globe, affecting 60% to 90% of school children and most adults, and producing discomfort that affects quality of life. Dental amalgam is frequently used to treat carious lesions and its use releases mercury into the environment. The best way to avoid the use of dental amalgam is to emphasize caries prevention. Alternatives to amalgam are suitable in some applications, but no replacement for amalgam has been found for large posterior restorations. For any restorative material, safety and environmental impacts are part of clinical risk assessment. Safety is freedom from unacceptable risks. Risk is a combination of probability of exposure and severity of harm. Best management practices are crucial to manage dental amalgam, but these impose additional that are disproportionately more for developing countries. The Minamata Convention seeks a phase-out of all mercury-based products except dental amalgam, where a phase-down is the present goal. For dentistry, the most important focus is the promotion of caries prevention and research on new materials.

The Minamata Convention, a global legally binding instrument (treaty) on mercury, has been the catalyst for the emerging agenda on global dental materials research. If the current and future challenges of oral health maintenance and healing on a global scale are to be met, a logical and effective research agenda for the discovery and introduction of new, environmentally sustainable, dental materials must be developed through a coordinated effort involving materials scientists, dental clinicians, representatives of industry, members of regional and national regulatory bodies, and advocacy from research organizations. For universal impact, this agenda should be created with awareness of several important ongoing initiatives, such as the WHO non-communicable diseases action plan, the UN sustainable development agenda, and the IADR Global Oral Health In Inequalities Research Agenda (GOHIRA). A significant contributor to this cause is the FDI and its membership, who, through their Vision 2020 initiative, acknowledge their role and responsibility in globally preventing and managing dental disease and providing leadership to the profession in terms of information dissemination and affecting change. Dental researchers also have an obligation to advocate for appropriate funding to match the identified research needs, thus enhancing the possibility that key decision-makers will provide the needed support to achieve the research agenda agreed upon by this diverse group of stakeholders.

This article outlines the subjects presented and discussed at the December 2012 IADR Dental Materials Innovation Workshop held at King's College London. Incorporating new materials and techniques into clinical practice was considered from 4 perspectives: (1) Accelerating the "research to regulatory approval" process was presented with current developments in the United States, with the National Institutes of Health/Food and Drug Administration process as a working example; (2) intellectual property and regulatory requirements were discussed across the well-established US and EU frameworks, as well as the more recently developed procedures across Brazil, Russia, India, and China; (3) the challenges and opportunities of incorporating innovations into dental education were considered with reference to the future needs of both students and faculty; and (4) the key but difficult and unpredictable step of translating such innovations into routine dental practice was then explored. Constructive and far-ranging discussion among the broadly based Workshop participants (from dental research, education, practice, and industry, as well as environmental organizations and the World Health Organization) mapped out key issues for the future. The focus was on facilitating the more timely adoption of improvements in both materials and techniques to improve patient health and health systems, while minimizing environmental impact.