Faculty Bibliography

Excessive scar or keloid shares common features of a benign dermal growth. Yet, in contrast to malignant tumor, a keloid does not expand beyond the dermis. What triggers the continuing growth of a benign lesion? Deficient or overabundant levels of vascular endothelial growth factor have been reported to contribute to impaired or excessive wound healing. Although numerous studies have examined the pathophysiology of impaired wounds, little information has been provided on mechanisms of exuberant healing. The molecular basis of keloid formation is governed by the interplay of cellular signaling pathways, specific target gene activation, and the nature of the microenvironment. Recent works have demonstrated an accumulation of hypoxia-inducible factor-1alpha protein in freshly biopsied keloid tissues, thus providing first evidence that a local state of hypoxia exists in keloids. Our findings and the findings of others support at least two plausible mechanisms implicated in the development of fibrotic wounds, a state of ongoing fibroplasia or inflammation and an excessive accumulation of extracellular matrix. This article will review recent works examining the potential role of vascular endothelial growth factor in keloid pathogenesis with particular focus on its involvement in the two proposed pathological processes, a prolonged inflammation and an altered balance in extracellular matrix metabolism

Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1alpha protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1alpha (HIF-1alpha) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1alpha may be a novel therapeutic target to modulate the scar fibrosis process

Understanding the role and importance of research and scholarship in dental education and practice requires an appreciation of dentistry as a learned profession. A foundational attribute for the members of such a profession has to be sheer intellectual curiosity--a trait as important for the clinician as for the scientist. That improved patient care results from technical advances made possible through research is not seriously disputed by anyone. What is less apparent, however, is the role for research in the education of dentists and in the broader life of dental schools. Accosting this matter requires a distinction to be made between research and scholarship: while all research qualifies as scholarship, not all scholarship qualifies as research. Though the exact role of research in the educational process is open to debate, the importance of scholarship is not. An education colored by research is one way of achieving the intellectual rigor necessary for the professional. The key is cultivating in students a taste for complexity, for problems, and for problem solving. All dental schools without exception need to help students acquire this taste. In doing so, they will generate a few scientists; but, more importantly, they will create out of every graduate a man or woman of science. Only by becoming a person of science is there any hope that the practitioner will be able to acquire and assimilate new knowledge and to adapt to the changes in practice and in the profession that the future requires

The premise of this paper is that the form and content of dental education do not reinforce each other. What results is suboptimal learning; dissatisfied students; difficulty generating excitement among the brightest to consider careers in dental education; erosion of dentists' self-identity as men and women of science; and doubts over whether dental schools can continue as the primary providers of oral health education. A need for reform exists because dental curricula must be responsive to changes in current and projected disease demographics, to advances in science and technology, and to a changing societal culture affecting patient demand for treatment. Today's dilemma is that dental schools need to continue to graduate competent practitioners to meet present clinical needs while also preparing students for a radically different kind of practice in the future. Possible approaches to resolve this dilemma include: a shift between what constitutes general practice and what constitutes specialty practice; and, the implementation of an asynchronous-distributed model of dental education. Such changes will likely be independently accompanied by changes in the role of universities in society in general that could make feasible many, now-unthinkable, alternative vehicles for providing dental education

Surgical correction of unilateral coronal synostosis offers a unique opportunity to examine the molecular differences between an abnormal and a normal cranial suture. We isolated and identified a cDNA fragment whose expression was up-regulated in the premature fusing and fused coronal sutures, as compared with normal coronal sutures. The nucleotide sequence of the full-length cDNA of this gene, human NELL-1, has approximately 61% homology with the chicken Nel gene. Both chicken Nel and human NELL-1 are comprised of six epidermal growth factor-like repeats. The human NELL-1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion. Human multiorgan tissue mRNA blot showed that NELL-1 was specifically expressed in fetal brain but not in fetal kidney, liver, or lung. We also showed that Nell-1 was expressed in rat calvarial osteoprogenitor cells and was largely absent in rat tibiae and fibroblast cell cultures. In conclusion, our data suggest that the NELL-1 gene is preferentially expressed in cranial intramembranous bone and neural tissue (both of neural crest cell origin) and is up-regulated during unilateral premature closure of the coronal suture. The precise role of this gene is unknown