Australian Dental Journal

The official journal of the Australian Dental Association

Australian Dental Journal 2014; 59:(1 Suppl): 1–5 doi: 10.1111/adj.12157

The face, the future, and dental practice: how research in craniofacial biology will influence patient care GC Townsend,* AH Brook*† *School of Dentistry, The University of Adelaide, South Australia, Australia. †Institute of Dentistry, Queen Mary University of London, United Kingdom.

ABSTRACT It has been a privilege to assemble a group of Australian and international researchers to produce a special issue of the Australian Dental Journal that reflects the cutting edge of research in different aspects of craniofacial biology, and also considers how these advances will influence future education and practice within dentistry. The aim of this special issue is to provide a collection of concept papers and critical reviews on key topics that cover both fundamental and applied research in craniofacial biology and to consider the clinical implications. To do this, four questions have been addressed that lead to the four sections of this issue. These are:

(1) How have we come to the present exciting position in craniofacial biology with breakthroughs over the past 50 years? (2) What are current fundamental research topics that are helping us to understand more about craniofacial and general development, possibly leading to future clinical developments? (3) What are the current applied research topics that will influence future clinical practice? (4) Looking forward, what new developments in craniofacial biology may come about that will change the face of dental education and practice? The refereed papers in this special issue are grouped into the four sections that seek to respond to these demanding questions. Keywords: Dentistry, teeth, research, genomics, epigenetics, phenomics.

INTRODUCTION In devoting an entire special issue of the Australian Dental Journal to the topic of craniofacial biology, the Editor and the Editorial Advisory Board are emphasizing to the profession that this is a major direction in which they see dentistry moving. We hope that the readership of the Journal will spend time going through the papers and reflect on their own practice of dentistry as it is at present, as well as considering where it is likely to go in the future. This issue builds on two previous volumes, one that arose from an international workshop on orofacial growth and development that was held in Liverpool, UK in 2007,1 and the other from a symposium held during a combined meeting of the International Union of Anthropological and Ethnological Sciences, the Australian Anthropological Society and the Association of Social Anthropologists of Aotearoa New Zealand at the University of Western Australia in 2011.2 © 2014 Australian Dental Association

A recent report of a meeting in the Journal of Dental Research also serves to highlight the advances being made in the field of craniofacial biology and how these discoveries are being translated into therapies that are based on an individual’s specific genetic profile.3 Section 1 – How have we come to the present exciting position with breakthroughs over the past 50 years? In the first paper of this issue, Geoffrey Sperber and his son, Steven, draw on their own extensive experience and the published literature, to provide a concise summary of the genesis of craniofacial biology as a distinct health science discipline.4 The key messages that come through in this paper are the tremendous scope of craniofacial biology, its relatively rapid development as a key discipline within the health sciences, including dentistry, and its implications for the 1

GC Townsend and AH Brook future practice of dentistry as we move towards new diagnostic and preventive approaches to manage oral diseases. The broad scope of topics that fall under the title of craniofacial biology means that an interdisciplinary approach is required for most research initiatives, to take advantage of the discoveries that have occurred in various areas, including molecular biology, biochemistry and paleo-anthropology, and also to make use of the various technologies that are available, including different imaging techniques. Section 2 – What are current fundamental research topics that are helping us to understand more about craniofacial and general development, possibly leading to future clinical developments? Most readers will be familiar with Chaos Theory and the concept of a butterfly fluttering its wings in South America and causing a storm in a distant part of the world – and some may have heard of Complexity Theory or Dynamic Systems Analysis. These theoretical models have been used to explain the complex dynamic nature of many systems in the world, including social systems, economies and ecosystems. It is important in this regard to differentiate ‘complex’ from ‘complicated’ and this distinction is discussed by the authors of the first paper in this section.5 An international team of researchers explain how both general and craniofacial development display the properties of a Complex Adaptive System, and they provide a detailed account of dental development as a Complex Adaptive Process. While the paper is theoretical, the authors explain that approaching development in this way provides a framework for investigating why there may be variations in phenotypes even though genotypes are identical, and they also describe how minor developmental disturbances may lead to major differences in phenotypic expression. A few years after the completion of the Human Genome Project, the journal Science announced that ‘epigenetics’ was the ‘breakthrough of the year’. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is still in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression and, potentially, susceptibility to oral disease. Researchers from Adelaide and Sydney provide a critical review of the field of epigenetics aimed specifically at oral health professionals in the second paper in this section.6 They define epigenetics, addressing its underlying concepts, and provide details about specific epigenetic molecular mechanisms. Furthermore, there is discussion of some of the key areas where epigenetics is implicated, and a review of some of the literature on epigenetics 2

research in dentistry, including the areas of periodontology, orthodontics, developmental defects and behaviour management. This review considers some implications of epigenetics for the future of dental practice, including a ‘personalized medicine’ approach to the management of common oral diseases. Phenomics has been defined as ‘the acquisition of high-dimensional phenotypic data on an organismwide scale’ and has progressed significantly in various fields over the past decade. Dental phenomics is an over-arching research field that involves measurement of variations in teeth and associated orofacial structures arising from interactions between genetic, epigenetic and environmental factors during development. In the next paper in this section, a team of researchers from Australia and the UK explain how advances in measuring dental phenotypes can enhance our understanding of the relationship between the genome, the epigenome and development.7 They also show how accurate quantification of changes in dental tissues can guide clinical diagnosis and treatment provision, as well as providing data for clinical research. This paper focuses on phenotyping of common oral diseases, including dental caries, periodontal disease, and craniofacial development. Irma Thesleff’s research team in Helsinki, Finland is recognized as a world leader in developmental biology related to dental development. Indeed, the patterns of approximately 300 genes involved in dental development can be viewed in the ‘Bite-it’ database (http:// bite-it.helsinki.fi). In her paper, Irma explains that there are sets of transient signalling centres in the dental epithelium that play important roles in the programme of tooth development.8 These signalling centres produce more than a dozen different signals locally and these signals belong to the bone morphogenetic protein, fibroblast growth factor, hedgehog and Wnt signal families. While current knowledge on tooth development is already being used in the diagnosis of some dental defects, advances in this field are likely to lead to novel approaches to the prevention of various orofacial disorders, including hypodontia associated with ectodermal dysplasia. There are also now definite possibilities for regenerating dental tissues and perhaps even bioengineering whole new teeth. The following two papers by leading researchers from internationally recognized research laboratories in the Czech Republic and France provide a fascinating review of the processes that occur during dental development.9,10 As students, we learnt about the dental lamina, the enamel organ and various other histological features, but Renata Peterkova, Herve Lesot and their research teams bring the process of dental development to life by combining 2D and 3D imaging with more classical histological methods. Drawing on knowledge of comparative odontology © 2014 Australian Dental Association

The face, the future, and dental practice and evolution, together with the use of very informative figures, they provide a new perspective of the stages of dental development from initiation to crown histogenesis. These papers offer a wonderful opportunity for readers to revisit a topic of fundamental importance to dentistry and to visualize the process of tooth formation in a completely new light. The discussion of supernumerary teeth is fascinating, with important implications for the possibility of regenerating teeth. The next paper describes an ongoing long-term study of teeth and faces of twins being carried out at the Adelaide School of Dentistry that began over 30 years ago.11 It emphasizes the value of twin studies as a means of untangling the influences of genetic, epigenetic and environmental factors on dentofacial features. The paper also highlights the value of collecting longitudinal data from human populations, despite the inherent difficulties, when attempting to understand more about the factors influencing physical growth and development. The large collection of records housed in the Adelaide School of Dentistry continues to serve as a unique resource for researchers from both dental and anthropological backgrounds. The authors stress that, as we move into a molecular era including genomics and epigenomics, studies of twins remain very relevant and, indeed, have certain advantages over other study designs. The last paper in this section provides a comprehensive review of stem cells, tissue engineering and periodontal regeneration.12 The senior authors, Stan Gronthos and Mark Bartold, have international reputations for their work on stem cells and it was Stan Gronthos with other co-researchers who coined the acronym ‘SHED’ in a paper in the Proceedings of the National Academy of Sciences in 2003 to refer to Stem cells from Human Exfoliated Deciduous teeth. The authors focus on the clinical utility of stem cells in periodontal regeneration and consider how the main stem cell types have been used. They emphasize that periodontal regeneration requires consideration of several factors associated with periodontal development, including the use of an optimal progenitor cell population, appropriate signalling molecules and a matrix scaffold that all need to be used in an orderly sequence. They also spell out several key objectives that will need to be addressed before cellular-based therapies for regenerative dentistry can become a reality. Section 3 – What are the current applied research topics that will influence future clinical practice? This section begins with a paper that applies the foundational topics discussed in the previous section. An international group of investigators explore how genetic, epigenetic and environmental influences during © 2014 Australian Dental Association

morphogenesis lead to variations in tooth number, size and shape.13 The advances in dental phenomics described in the last section have important applications in advancing genotype-phenotype correlations to enhance understanding of clinically important variations and anomalies. This understanding of dental development alerts the clinician to the presentation together of these conditions in the patient. The epidemiological and clinical basis for this was confirmed and modelled by Alan Brook in 1984 and more recent developmental studies have provided the genetic explanation of the associations of these clinical phenotypes. Thus, the molecular evidence of repetitive signalling throughout initiation and morphogenesis is reflected clinically in the association of anomalies of number, size and shape. Early diagnosis allows optimal patient management and treatment planning with intervention at an appropriate time to prevent complications during development and so reduce later treatment need. Understanding the process of dental morphogenesis and the variations in the outcomes is an important contribution to the multidisciplinary clinical team approach to patient care. Combining accurate clinical observation and measurement with fundamental investigations is advancing both understanding and clinical care. Kim Seow explains in her paper that, although the clinical significance of defects of enamel and dentine are well known, the pathogenesis of these defects is still being actively studied.14 She discusses some of the advances that have occurred in understanding which genes are involved in enamel and dentine defects and also describes some of the environmental insults that can affect dental development. The clinical presentations of dental enamel defects are described, including discolouration, tooth sensitivity, and susceptibility to caries, wear and erosion. The complications of dentine defects are also explored, including the need for endodontic management. Despite major advances in knowledge about the causes of enamel and dentine defects, Kim notes that further research is needed in order to translate basic science knowledge to accurate clinical diagnosis and successful treatment of these defects. In the next paper in this section, Jules Keiser and a team of researchers from New Zealand and Germany describe ongoing research that they are carrying out involving recording tongue pressures in healthy subjects during normal oral activities such as mastication, speech and swallowing.15 They point out that most research to date has focused on the generation of positive pressure by the tongue on the hard palate and the teeth, while coordination of absolute intraoral pressures and regional pressure gradients have been largely overlooked. Their research has shown highly variable individual patterns of tongue pressure during swallowing 3

GC Townsend and AH Brook that can be broadly classified into four stages. This innovative research is providing a foundation for future studies into the effects insertion of oral appliances or the use of maxillary expansion approaches. The work also promises to throw light on the effects of neuromuscular conditions, such as Parkinson’s and Huntington’s diseases, muscular dystrophy and cerebral palsy, on the motor functions of the tongue. It is very interesting to see how two different disciplines, anthropology and clinical dentistry, view the topic of dental occlusion, and how their differing perspectives can be drawn together to provide a more comprehensive understanding of such a fundamental topic. John Kaidonis and his colleagues from Adelaide have been influenced greatly by the rich tradition of dental anthropology that has existed in the Adelaide Dental School, from Thomas Draper Campbell in the early 1900s through to Murray Barrett and Tasman Brown in the later part of the 20th century. In their concept paper, it is proposed that modern human populations living in industrialized environments display dental occlusions that can be considered as ‘neotenous’, meaning that our dentitions tend to reflect an unworn stage which in our ancestors was only evident in young individuals.16 The authors propose that clinicians need to be able to draw on evolutionary and developmental perspectives of ‘functional dental occlusion’ to differentiate between continual physiological changes in the masticatory system that tend to occur over time and require ongoing review but often no treatment, compared with pathological responses in the system that require intervention. There have been tremendous advances in the field of three-dimensional diagnostic imaging since the invention of the first computed tomography (CT) scanner in the early 1970s. These advances have led to a wide range of applications in craniofacial clinical practice and research. In the final paper in this section, Peter Anderson from the Australian Craniofacial Unit and colleagues from Malaysia and Adelaide provide an overview of 3D CT imaging technology, as well as discussing current and future prospects of different CT modalities in dentistry.17 Medical CT has an important role in the diagnosis and management of craniofacial injuries and pathology, while 3D conebeam CT is being used increasingly in dentistry. Some of the applications of micro-CT in craniofacial biology research are also discussed, together for its potential for translational clinical research. Section 4 – Looking forward, what new developments in craniofacial biology may come about that will change the face of dental education and practice? Hal Slavkin has been a world leader in dental education and research for decades, and is a ‘father figure’ 4

in the field of craniofacial biology. We are very pleased that he has provided his thoughts on the future of research in craniofacial biology and the implications for clinical practice and professional education in this special issue. In the final paper of this special issue, Hal anticipates that, in the future, clinicians will play a major role in identifying clinical phenotypes to improve differential diagnosis, as well as in rejuvenating missing or damaged tissues based on gene-based diagnostics and biomimetic approaches.18 He predicts that there will need to be an increased emphasis in dental education on developing critical thinking and being able to access and analyse databases that are relevant to clinical health care. Hal also envisions oral health becoming more integrated into primary health care and family medicine. SUMMARY In deciding on the topics to be covered in this special issue, we were well aware that the main target group of readers of the Australian Dental Journal is the Australian dental profession, including general dentists, specialists and oral health professionals. We wanted a strong international flavour to the issue and to invite some of the world’s leading researchers and academics in the field of craniofacial biology to contribute. We were also aware that the series of special issues in the Australian Dental Journal serve as valuable resources for undergraduate and postgraduate students, not only within Australia, but also internationally. We have included a mix of concept and review papers, together with some original research findings that we believe are exciting, challenging and informative. Our aim is that this issue will not only provide a stimulus to future research but also serve as a guide to the future directions of dental education and practice. ACKNOWLEDGEMENTS We would like to thank the peer reviewers of the papers in this special issue for their very helpful comments and suggestions. We would also like to acknowledge the outstanding efforts of Karen Squires, School of Dentistry, The University of Adelaide, and the Australian Dental Journal’s Senior Production Editor, Helen Pontikis, in putting this special issue together. REFERENCES 1. Brook AH. Editorial. Research collaboration initiative. Arch Oral Biol 2009;54S:S1–S2. 2. Townsend GC, Kanazawa E, Takayama H. New directions in dental anthropology: paradigms, methodologies and outcomes. Adelaide: University of Adelaide Press, 2012. © 2014 Australian Dental Association

The face, the future, and dental practice 3. D’Souza RN, Dunnvald M, Frazier-Bowers S, et al. Translational genetics: advancing fronts for craniofacial health. J Dent Res 2013;9:1058–1064. 4. Sperber GH, Sperber SM. The genesis of craniofacial biology as a health science discipline. Aust Dent J 2014; doi:10.1111/adj. 12131 [Epub ahead of print]. 5. Brook AH, Brook O’Donnell M, Hone A, et al. General and craniofacial development are complex adaptive processes influenced by diversity. Aust Dent J 2014; doi:10.1111/adj.12158 [Epub ahead of print]. 6. Williams SD, Hughes TE, Adler CJ, Brook AH, Townsend GC. Epigenetics: a new frontier in dentistry. Aust Dent J 2014; doi:10.1111/adj.12155 [Epub ahead of print]. 7. Yong R, Ranjitkar S, Townsend GC, et al. Dental phenomics: advancing genotype to phenotype correlations in craniofacial research. Aust Dent J 2014; doi:10.1111/adj.12156 [Epub ahead of print]. 8. Thesleff I. Current understanding of the process of tooth formation: transfer from the laboratory to the clinic. Aust Dent J 2013; doi:10.1111/adj.12102 [Epub ahead of print]. 9. Peterkova R, Hovorakova M, Peterka M, Lesot H. Three-dimensional analysis of the early development of the dentition. Aust Dent J 2014; doi:10.1111/adj.12130 [Epub ahead of print]. 10. Lesot H, Hovorakova M, Peterka M, Peterkova R. Threedimensional analysis of molar development in the mouse from the cap to bell stage. Aust Dent J 2014; doi:10.1111/adj.12132 [Epub ahead of print]. 11. Hughes TE, Townsend GC, Pinkerton SK, et al. The teeth and faces of twins: providing insights into dentofacial development and oral health for practising oral health professionals. Aust Dent J 2013; doi:10.1111/adj.12101 [Epub ahead of print]. 12. Han J, Menicanin D, Gronthos S, Bartold PM. Stem cells, tissue engineering and periodontal regeneration. Aust Dent J 2013; doi:10.1111/adj.12100 [Epub ahead of print].

© 2014 Australian Dental Association

13. Brook AH, Jernvall J, Smith RN, Hughes TE, Townsend GC. The dentition: the outcomes of morphogenesis leading to variations of tooth number, size and shape. Aust Dent J 2014; doi:10.1111/adj.12160 [Epub ahead of print]. 14. Seow WK. Developmental defects of enamel and dentine: challenges for basic science research and clinical management. Aust Dent J 2013; doi:10.1111/adj.12104 [Epub ahead of print]. 15. Kieser JA, Farland MG, Jack H, Farella M, Wang Y, Rohrle O. The role of oral soft tissues in swallowing function: what can tongue pressure tell us? Aust Dent J 2013; doi:10.1111/adj. 12103 [Epub ahead of print]. 16. Kaidonis JA, Ranjitkar S, Lekkas D, Brook AH, Townsend GC. Functional dental occlusion: an anthropological perspective and implications for practice. Aust Dent J 2014; doi:10.1111/adj. 12133 [Epub ahead of print]. 17. Anderson PJ, Yong R, Surman TL, Rajion ZA, Ranjitkar S. Application of three-dimensional computed tomography in craniofacial clinical practice and research. Aust Dent J 2014; doi:10.1111/adj.12154 [Epub ahead of print]. 18. Slavkin HC. The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice. Aust Dent J 2014; doi:10.1111/adj.12105 [Epub ahead of print].

Address for correspondence: Professor Grant Townsend School of Dentistry The University of Adelaide Adelaide SA 5005 Australia Email: [email protected]

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The face, the future, and dental practice: how research in craniofacial biology will influence patient care.

It has been a privilege to assemble a group of Australian and international researchers to produce a special issue of the Australian Dental Journal th...
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