Malformations of the tooth root in humans

The most common root malformations in humans arise from either developmental disorders of the root alone or disorders of radicular development as part of a general tooth dysplasia. The aim of this review is to relate the characteristics of these root malformations to potentially disrupted processes involved in radicular morphogenesis. Radicular morphogenesis proceeds under the control of Hertwig's epithelial root sheath (HERS) which determines the number, length, and shape of the root, induces the formation of radicular dentin, and participates in the development of root cementum. Formation of HERS at the transition from crown to root development appears to be very insensitive to adverse effects, with the result that rootless teeth are extremely rare. In contrast, shortened roots as a consequence of impaired or prematurely halted apical growth of HERS constitute the most prevalent radicular dysplasia which occurs due to trauma and unknown reasons as well as in association with dentin disorders. While odontoblast differentiation inevitably stops when growth of HERS is arrested, it seems to be unaffected even in cases of severe dentin dysplasias such as regional odontodysplasia and dentin dysplasia type I. As a result radicular dentin formation is at least initiated and progresses for a limited time. The only condition affecting cementogenesis is hypophosphatasia which disrupts the formation of acellular cementum through an inhibition of mineralization. A process particularly susceptible to adverse effects appears to be the formation of the furcation in multirooted teeth. Impairment or disruption of this process entails taurodontism, single-rooted posterior teeth, and misshapen furcations. Thus, even though many characteristics of human root malformations can be related to disorders of specific processes involved in radicular morphogenesis, precise inferences as to the pathogenesis of these dysplasias are hampered by the still limited knowledge on root formation

Abnormal mandibular growth and the condylar cartilage

Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their oftendisfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritits (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilag

Principles of cartilage tissue engineering in TMJ reconstruction

Diseases and defects of the temporomandibular joint (TMJ), compromising the cartilaginous layer of the condyle, impose a significant treatment challenge. Different regeneration approaches, especially surgical interventions at the TMJ's cartilage surface, are established treatment methods in maxillofacial surgery but fail to induce a regeneration ad integrum. Cartilage tissue engineering, in contrast, is a newly introduced treatment option in cartilage reconstruction strategies aimed to heal cartilaginous defects. Because cartilage has a limited capacity for intrinsic repair, and even minor lesions or injuries may lead to progressive damage, biological oriented approaches have gained special interest in cartilage therapy. Cell based cartilage regeneration is suggested to improve cartilage repair or reconstruction therapies. Autologous cell implantation, for example, is the first step as a clinically used cell based regeneration option. More advanced or complex therapeutical options (extracorporeal cartilage engineering, genetic engineering, both under evaluation in pre-clinical investigations) have not reached the level of clinical trials but may be approached in the near future. In order to understand cartilage tissue engineering as a new treatment option, an overview of the biological, engineering, and clinical challenges as well as the inherent constraints of the different treatment modalities are given in this paper

Appearance of affected primary teeth in calibrated backscattered electron images and a light micrograph.

<p>(<b>A</b>): Overview of maxillary incisor crown disclosing thin enamel (e) covering the dentin (d); rectangles mark the details shown in B and E. (<b>B</b>, <b>C</b>): In comparison to healthy enamel (<b>C</b>), enamel (e) from the affected tooth (<b>B</b>) exhibits wide, dark-gray borders between the prisms (arrows) and is covered by thin, mineralized deposits, presumably coronal cementum (asterisks). (<b>D</b>): These deposits (asterisks), in turn, are covered by dental plaque (dp) stained intensely with toluidine blue. (<b>E</b>, <b>F</b>): Dentin from affected (<b>E</b>) and healthy (<b>F</b>) teeth exhibits similar proportions of light (densely mineralized) peritubular dentin (arrows) separating the broader intertubular dentin from the dentinal tubules, but both types of dentin appear darker (less mineralized) in affected teeth (<b>E</b>). Original magnifications (<b>A</b>): 80x, (<b>D</b>): 200x, (<b>B</b>, <b>C</b>, <b>E</b>, <b>F</b>): 3000x.</p

Mineral Density across Enamel and Dentin of Control and Affected Teeth.

<p>The distance scale is normalized with respect to the average thickness of healthy enamel and dentin; as a result, the surface of a normal tooth corresponds to 0%, the dentin-enamel-junction to 100%, and the dentin-pulp-border to 200%. The thickness of affected (CRD/AI) enamel corresponds to the average across all specimens examined; mineral densities to the left of affected enamel concern deposits on the surface. For the affected teeth, estimates from the two sites of each tooth are plotted as dotted and solid lines of the same color; note the large variation between and within individual CRD/AI teeth, which was significantly (p = 0.03) higher than in control specimens.</p

Appearance of the teeth in the two affected brothers.

<p>(<b>A</b>-<b>C</b>): Yellow-brown discolored primary teeth of the elder boy at the age of 6 years; white arrow points at the maxillary incisor shown microscopically in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078529#pone-0078529-g002" target="_blank">Figure 2</a>. (<b>D</b>): Groove-shaped enamel hypoplasias in primary teeth of the younger boy at the age of 2 years 11 months. (<b>E</b>, <b>F</b>): Dental enamel cannot be distinguished from dentin in the panoramic radiographs taken from the elder boy at 4 years 7 months (<b>E</b>) and 10 years 6 months of age (<b>F</b>); large pulp cavities seen during eruption of permanent teeth (<b>E</b>) become normal, after teeth are in occlusion (<b>F</b>).</p

Dental phenotype in Jalili Syndrome due to a c.1312 dupC homozygous mutation in the CNNM4 gene

Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy) and a dental disorder (amelogenesis imperfecta), which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a disrupted magnesium transport is involved in the development of the dental abnormalities observed in Jalili syndrome