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Biomedical subjects

Harold C Slavkin

Publications and source records attributed to Harold C Slavkin.

13 recordsLinked to original sources
PubMed2005

LEF1 is a critical epithelial survival factor during tooth morphogenesis.

LEF1 is a cell-type-specific transcription factor and mediates Wnt signaling pathway by association with its co-activator beta-catenin. Wnt signaling is known to be critical for the specification of cranial neural crest (CNC) cells and may regulate the fate diversity of the CNC during craniofacial morphogenesis. Loss of Lef1 results in arrested tooth development at the late bud stage and LEF1 is required for a relay of a Wnt signaling to a cascade of FGF signaling activities to mediate the epithelial-mesenchymal interaction during tooth morphogenesis. It remains unclear, however, what is the cellular mechanism of LEF1 signaling in regulating tooth morphogenesis. To test the hypothesis that LEF1 signaling regulates the fate of the dental epithelial and the CNC-derived mesenchymal cells during tooth morphogenesis, we investigated and compared the cellular migration, proliferation, and apoptotic activity within the tooth germ between the wild-type and Lef1 null mutant mice. Using the Wnt1-Cre/R26R transgenic system for indelibly marking the progenies of CNC cells, we show that there is no CNC migration defect in the Lef1 null mutant mice, indicating that the arrest in tooth development is not the result of shortage of the CNC contribution into the first branchial arch in the Lef1 mutant. Furthermore, there is no alteration in cell proliferation or condensation of the CNC-derived dental mesenchyme in the Lef1 null mutant, suggesting that LEF1 may not affect the cell cycle progression of the multipotential CNC cells during tooth morphogenesis. Importantly, apoptotic activity is significantly increased within the dental epithelium in the Lef1 null mutant mice. As the result of this increased cell death, the bud stage tooth germ fails to advance to the cap stage in the absence of Lef1. Inhibition of apoptotic activity by FGF4 rescues the tooth development in the Lef1 null mutant. Our studies suggest that LEF1 is a critical survival factor for the dental epithelial cells during tooth morphogenesis.

Animals↗
PubMed2004

Reforming dental health professions education: a white paper.

The oral health education system is in need of major reform! This is especially apparent in university-based education for the health professions. So-called preclinical as well as clinical education simply has not kept pace with or been responsive enough to shifting patient demographics and patient/population desires and expectations, changing health system expectations, evolving interdisciplinary expertise and practice requirements, new scientific discoveries and scientific information, focus on quality improvement, and/or integration of emerging technologies. Moreover, university-based "dental education" is the most costly professional degree education within the entire university portfolio, and dental student accumulated debt is increasing each year well beyond national inflation estimates. Today, we have an enormous opportunity to explore major reforms in health professional education. Through the Santa Fe "process" of open and candid engagements and discussions (see www.santafegroup.org), we advance an argument as well as a national strategy that can enable major reforms in the oral health education system. We further suggest that major revisions can result in an outcome-based education system that prepares oral health professionals to meet both the needs of patients/families/communities and the requirements of a changing health system.

Clinical Competence↗
PubMed2003

Prospects for tooth regeneration in the 21st century: a perspective.

The prospects for tooth regeneration in the 21st century are compelling. Using the foundations of experimental embryology, developmental and molecular biology, the principles of biomimetics (the mimicking of biological processes), tooth regeneration is becoming a realistic possibility within the next few decades. The cellular, molecular, and developmental "rules" for tooth morphogenesis are rapidly being discovered. The knowledge gained from adult stem cell biology, especially associated with dentin, cartilage, and bone tissue regeneration, provides additional opportunities for eventual tooth organogenesis. The centuries of tooth development using xenotransplantation, allotransplantation, and autotransplantation have resulted in many important insights that can enhance tooth regeneration. In considering the future, several lines of evidence need to be considered: (1) enamel organ epithelia and dental papilla mesenchyme tissues contain stem cells during postnatal stages of life; (2) late cap stage and bell stage tooth organs contain stem cells; (3) odontogenic adult stem cells respond to mechanical as well as chemical "signals"; (4) presumably adult bone marrow as well as dental pulp tissues contain "odontogenic" stem cells; and (5) epithelial-mesenchymal interactions are pre-requisite for tooth regeneration. The authors express "guarded enthusiasm," yet there should be little doubt that adult stem cell-mediated tooth regeneration will be realized in the not too distant future. The prospects for tooth regeneration could be realized in the next few decades and could be rapidly utilized to improve the quality of human life in many nations around the world.

Dentistry, Operative↗
PubMed2003

Insulin-like growth factors, hepatocyte growth factor and transforming growth factor-alpha in mouse tongue myogenesis.

Many reports have shown that tongue striated muscles have several unique characteristics not found in other skeletal muscles such as limb and trunk. Several peptide growth factors are reported to play important roles in skeletal myogenesis. In this article, the roles of insulin-like growth factors (IGF), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha in mouse tongue myogenesis were studied using an organ culture system of the mandible or tongue obtained from mouse embryos. It was found that IGF-I promotes the differentiation of tongue myoblasts. HGF plays an essential role in the migration and proliferation of tongue myogenic cells, and inhibits the differentiation of tongue myoblasts. TGF-alpha does not play an essential role in the proliferation of tongue myogenic cells, but does promote the early differentiation of tongue myoblasts. The role of IGF-I in the differentiation of tongue myoblasts, and that of HGF in the migration, proliferation and differentiation of tongue myogenic cells appear to be almost identical to their roles in the myogenesis of limb and cultured myogenic cell lines. However, the role of TGF-alpha in the proliferation and differentiation of tongue myogenic cells appears to be different from its role in the myogenesis of limb and cultured myogenic cell lines such as C2 and L6.

Animals↗
PubMed2003

Applications of pharmacogenomics in general dental practice.

The human oral cavity represents a complex ecology of approximately 500 microbial species existing as commensals, and interacting with human/host factors. Perturbation of this ecosystem can lead to diseases of the oral cavity. The oral cavity also acts as a mirror of complex systemic diseases. Unique challenges and opportunities in oral healthcare exist in the diagnosis and treatment of primary disorders of the oral cavity or manifestations of systemic diseases. The completion of human and microbial genome projects has provided a wealth of information that will permit the application of pharmacogenomics - how genetic variations within the commensal and the host will impact the efficacy of drugs, and the diagnosis and treatment of oral disease. This review highlights opportunities focusing on oral health where pharmacogenomics can be applied.

Diagnosis, Oral↗
PubMed2002

Distinguishing Mars from Venus: emergence of gender biology differences in oral health and systemic disease.

We are learning to appreciate and understand that men and women have different genes and gene products (proteins), biochemistry and physiology, body weights and distribution of fats, and a few different tissues and organs. In such comparisons, we discover that women have a different prevalence for many oral and systemic diseases and disorders, and often illustrate differences in responses to disease mechanisms as well as to drug therapy and treatments. For example, consider the milestones of development, such as puberty or menopause, the unique differences in the prevalence of autoimmune diseases and disorders (Sjögren's syndrome, Hashimoto's disease), differences in the onset and progression of osteoporosis and osteoarthritis, differences in response to radiation and chemotherapy, and the differences in chronic facial pain, chronic fatigue syndrome, and fibromyalgia. This article highlights many opportunities to enhance the quality of oral health care for women.

Adult↗