Sonic Hedgehog Signaling and Development of the Dentition

Sonic hedgehog (Shh) is an essential signaling peptide required for normal embryonic development. It represents a highly-conserved marker of odontogenesis amongst the toothed vertebrates. Signal transduction is involved in early specification of the tooth-forming epithelium in the oral cavity, and, ultimately, in defining tooth number within the established dentition. Shh also promotes the morphogenetic movement of epithelial cells in the early tooth bud, and influences cell cycle regulation, morphogenesis, and differentiation in the tooth germ. More recently, Shh has been identified as a stem cell regulator in the continuously erupting incisors of mice. Here, we review contemporary data relating to the role of Shh in odontogenesis, focusing on tooth development in mammals and cartilaginous fishes. We also describe the multiple actions of this signaling protein at the cellular level

National British Orthodontic Society (BOS) Orthognathic Audit 2017-2018

OBJECTIVE: To carry out a UK national clinical audit of orthognathic acceptance criteria and information provided to orthognathic patients before treatment. DESIGN: National clinical audit. SETTING: Data collected using Bristol Online Surveys. PARTICIPANTS: Sixty-nine UK hospital orthodontic departments submitted data. METHODS: Data were collected at two time points using Bristol Online Surveys over a period of 12 months. These were before treatment at the first multidisciplinary clinic (MDT) and immediately after surgery. The data collected included: Index of Orthognathic Functional Treatment Need (IOFTN); Index of Orthodontic Treatment Need (IOTN); age; previous orthodontic treatment; attendance at an MDT; treatment times; and information provision. RESULTS: Eighty-five units agreed to take part in the audit with 69 submitting data, giving a response rate of 81%. The data from 3404 patients were uploaded, 2263 before treatment and 1141 immediately after surgery. Of patients, 91.07% had an IOFTN score of 4 or 5 and 88.73% had an IOTN score of 4 or 5. The mean age at the first MDT was 22 years in the first cohort and 21 years and 4 months in the second immediate post-surgery cohort. Of patients, 37.93% had undergone some form of previous orthodontic treatment, but only 0.28% had undergone previous orthognathic treatment; 96.93% had an MDT confirm that orthodontic treatment by itself was insufficient to adequately correct their functional symptoms. The average treatment time from bond up to surgery was 2 years and 6 months. With respect to information provision, patients received information from a number of sources, principally the British Orthodontic Society (BOS) patient information leaflets and the BOS website Your Jaw Surgery. CONCLUSIONS: In the UK, the majority of orthognathic cases fulfil the criteria for acceptance for NHS-funded orthognathic treatment, as outlined by the Chief Dental Officer's interim guidance on orthognathic treatment. This suggests any prior approval process would not be a good use of NHS resources in the commissioning of orthognathic treatment

National BOS Orthognathic Audit 2017-2018

Objective; To carry out a UK national clinical audit of orthognathic acceptance criteria and information provided to orthognathic patients prior to treatment. / Design; National clinical audit. / Setting; Data collected using Bristol Online Surveys (BOS). / Participants; 69 UK hospital orthodontic departments submitted data. / Methods; Data was collected at two time points using BOS over a period of 12 months. These were prior to treatment at the first multidisciplinary clinic (MDT), and immediately post-surgery. The data collected included: IOFTN, IOTN, age, previous orthodontic treatment, attendance at an MDT, treatment times and information provision. / Results; 85 units agreed to take part in the audit with 69 submitting data, giving a response rate of 81%. The data from 3404 patients were uploaded, 2263 prior to treatment and 1141 immediately post-surgery. 91.07% of patients had an IOFTN score of 4 or 5 and 88.73% had an IOTN score of 4 or 5. The mean age at the first MDT was 22yr in the first cohort, and 21yr and 4mo in the second immediate post-surgery cohort. 37.93% of patients had undergone some form of previous orthodontic treatment, but only 0.28% had undergone previous orthognathic treatment. 96.93% had a multidisciplinary team confirm that orthodontic treatment by itself was insufficient to adequately correct their functional symptoms. The average treatment time from bond up to surgery was 2yr and 6mo. With respect to information provision, patients received information from a number of sources, principally the BOS patient information leaflets and the BOS website Your Jaw Surgery. / Conclusions; In the UK, the majority of orthognathic cases fulfil the criteria for acceptance for NHS funded orthognathic treatment, as outlined by the Chief Dental Officer’s interim guidance on orthognathic treatment. This suggests any prior approval process would not be a good use of NHS resources in the commissioning of orthognathic treatment

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study

Introduction: Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities.To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies.Methods: Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13th and 30th weeks of gestation fulfilled the parameters to autopsy.Results: Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13th week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia).Conclusions: This results indicateinfo:eu-repo/semantics/publishedVersio

Lrp4 Modulates Extracellular Integration of Cell Signaling Pathways in Development

The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway

Gene-enhanced tissue engineering for dental hard tissue regeneration: (1) overview and practical considerations

Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration