Sven Lindskog

Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous system.

Abstract.Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-β family and has potent neurotrophic effects on several classes of neurons including dopamine neurons and motoneurons. Here, we have used in situ hybridization to describe the development of the cellular expression of GDNF mRNA pre- and postnatally. Consistent with dopaminotrophic activity, GDNF mRNA is expressed in the developing basal ganglia and the olfactory tubercle. It is also found in a thalamic nucleus, in neurons of the substantia innominata, in the developing Purkinje neurons and the developing locus coeruleus area, and in trigeminal brainstem nuclei. In the spinal cord, neuronal expression is found in Clarke’s column. GDNF mRNA is also expressed in the dorsal horns during development. Additional GDNF mRNA expression in the head region includes the carotid body, the retina, the vibrissae, the inner ear, the ear canal, and epithelium in the nasal cavity. Prominent expression is also found in the developing teeth. The widespread expression of GDNF in developing skeletal muscle is consistent with trophic activity on α-motoneurons. The smooth muscle layers of the gastrointestinal tract are also strongly positive. A very strong signal is found in the outer mesenchyme of the developing metanephric kidney. We conclude that GDNF mRNA is expressed in many different cellular systems inside and outside the central nervous system during development, suggesting multiple functions of GDNF in the developing organism.

Tooth ankylosis. Clinical, radiographic and histological assessments.

Ankylosis is a serious condition for the affected teeth as such teeth form part of the remodelling process of the alveolar bone and are therefore progressively resorbed. There are, however, very few clinical studies on tooth ankylosis and the reason for this may be due to the difficulties that are encountered in the diagnosis of minor areas of ankylosis. In the present study, the radiographs, percussion sound and mobility of experimentally extracted and replanted monkey incisors were compared with a morphometric histological study of ankylosis. Ankylotic areas were evident radiographically when the ankylosis was located on the proximal surfaces of the root, but were not evident when the ankylosis occurred on the lingual and labial surfaces. The percussion sound was dull and the mobility normal in all non-ankylotic teeth as well as in those teeth which histologically demonstrated ankylosis on less than 10% of the root surface. When the ankylosis affected 10-20% of the root surface, 2 out of 4 teeth changed their percussion sound from dull to high and these teeth no longer possessed normal mobility. When more than 20% of the root surface was affected with ankylosis, the percussion sound was characteristically high in all teeth and no mobility was present.

Storage of Experimentally Avulsed Teeth in Milk Prior to Replantation

Extracted monkey teeth were endodontically treated, stored in milk or saliva for two or six h, and then replanted. Periodontal conditions were evaluated after eight wk. Teeth that had been stored for two or six h in milk or for two h in saliva showed periodontal healing almost as good as that of immediately replanted teeth. Teeth that had been kept in saliva for six h or bench-dried for one h showed extensive replacement resorption. Milk may thus be recommended as a storage medium for ex-articulated teeth prior to replantation in cases when immediate replantation is not possible.

Influence of osmolality and composition of some storage media on human periodontal ligament cells.

The effect of media with different osmolalities and compositions on cell viability and integrity of the cell membrane has been studied. Physiologic media, such as milk, saline and physiologic sucrose solution, preserved cell viability and membrane morphology equally well. The cell membrane of cells stored in saliva was more extensively damaged than the cell membrane of cells stored in a sucrose solution with an hypotonic osmolality similar to saliva. Thus a hypotonic osmolality seemed to potentiate the damaging effect of an unfavourable composition or a bacterial contamination of the storage media.

Periodontal Healing of Replanted Monkey Teeth Prevented from Drying

Root resorption of replanted teeth is dependent on the duration of the extra-alveolar period and on the storage environment. In the present investigation the significance of preserving the humidity of the periodontal ligament (PDL) during the extra-alveolar period was tested on isolated PDL cells and on replanted monkey teeth. The isolated PDL cells were tested with respect to cell viability (trypan blue exclusion test) and to cell recovery (number of cells after additional cultivation). About 70% of the cells were viable and 44% recovered after 1 h in a humid atmosphere. Practically no cells were viable or recovered after 1 h of drying. Replanted teeth that had been wrapped in plastic foil for 1 h before replantation showed no more resorption than immediately replanted teeth. This is in contrast to teeth dried in air for 1 h before replantation. They showed extensive root resorption on almost all root surfaces. Thus, prevention of evaporation of tissue fluid from the PDL must be considered a primary goal if the tooth cannot be replanted immediately.

The effect of an antibiotic/corticosteroid paste on inflammatory root resorption in vivo

Progressive external inflammatory root resorption, a result of persistent inflammation within the periodontal membrane, will cause eventual destruction of the tooth root if the inflammation is not eradicated. This study examined the effects of an antibiotic/corticosteroid paste on experimental inflammatory resorption induced in monkeys in vivo. Histologic evaluation of results with the use of a morphometric technique revealed that the paste eliminated inflammatory root resorption and had no damaging effects upon the periodontal membrane. It was concluded that this antibiotic/corticosteroid combination is an effective medication for use in the treatment of progressive root resorption in traumatically injured teeth.

Cellular expression of neurotrophin mRNAs during tooth development

Abstract. Target-derived neurotrophins support and sustain peripheral sensory neurons during development. In addition, it has been suggested that these growth factors could have developmental functions in non-neuronal tissues. To further elucidate the possible roles of neurotrophins in tooth morphogenesis and innervation, we have used in-situ hybridization to determine the specific sites of neurotrophin gene activity in pre- and postnatal rat jaws from E16 to P7. All four neurotrophins were expressed during tooth development with specific temporospatial patterns. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNAs were mainly detected in the dental papilla/pulp in postnatal animals, and the pattern of expression correlated with the onset of dental innervation. In contrast, neurotrophin 3 (NT3) and neurotrophin 4 (NT4) mRNA expression patterns were predominantly epithelial and were strongest during early developmental stages when teeth are not yet innervated. Dental papilla NGF-mRNA expression was first seen in both epithelium and mesenchyme and later shifted to the odontoblast layer and the subodontoblast zone. BDNF-mRNA labeling was present in low levels in the early dental organ, but increased in the pulp and in the odontoblast cell layer of the developing teeth at later developmental stages. Both NT3 and NT4 mRNA were observed in the prenatal oral epithelium and the inner dental epithelium. NT3-mRNA labeling was seen mainly in the cervical loop region, fissure system depressions and cuspal tops, while NT4 mRNA was more evenly distributed in the dental epithelium. At P7, NT3-mRNA labeling was below detection level and NT4 mRNA expression was lower than at prior stages. Complementary to reports on the presence of low-affinity neurotrophin receptor (LANR), trkB and trkC mRNA in the developing teeth, our results suggest that neurotrophins may have multiple functions during tooth morphogenesis. Neurotrophins might participate in epithelial-mesenchymal interactions in early tooth morphogenetic events such as proliferation and differentiation of epithelial and mesenchymal cells. In addition, based on mRNA localization in postnatal animals, we also suggest that NGF and BDNF (beside glial cell line-derived neurotrophic factor) might participate in establishing and maintaining the innervation of the teeth, thus acting as classical neurotrophic factors.

Osteoclasts: Structure and function

Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major rôle in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease.

Calcitonin as an alternative therapy in the treatment of root resorption.

Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

Effect of a chemo-mechanical caries removal system (Carisolv) on dentin topography of non-carious dentin.

The purpose of the present study was to examine the morphology of healthy dentin surfaces after treatment with Carisolv followed by conditioning with phosphoric acid and EDTA, since surface morphology may be of interest for dentin bonding. Another purpose was to evaluate the effect of treatment with Carisolv on healthy non-carious dentin surfaces with exposed collagen fibers. Scanning electron microscopy was utilized to carry out a detailed morphological examination of the dentin surfaces with regard to presence or absence of both smear layer and collagen fibers. Twelve premolars extracted for orthodontic reasons from young adults were used. The two etchants appeared to have produced two distinctly different surfaces. Etching with phosphoric acid following Carisolv treatment resulted in a porous dentin surface, while EDTA etching without prior Carisolv treatment appeared to have uncovered an intact collagen network. In contrast, the surfaces treated with Carisolv prior to EDTA etching displayed smooth intertubular surfaces with only occasional fibers. Apparently, the ability of EDTA to expose collagen in the dentin surface is counteracted or inhibited by the Carisolv treatment. Furthermore, it cannot be excluded that the Carisolv treatment in itself may have dissolved collagen fibers. Since most bonding systems claim bonding to the collagenous component of dentin, the question arises which of the etched surfaces is preferable and to what degree the collagenous component contributes to bonding strength. Further studies are thus needed to evaluate the micromechanical retention of a restoration to the different surfaces described in the present study.