Biomedical subjects

W Götz

Publications and source records attributed to W Götz.

At least 19 recordsLinked to original sources

PubMed2006

Parathyroid hormone(1-34) mediates proliferative and apoptotic signaling in human periodontal ligament cells in vitro via protein kinase C-dependent and protein kinase A-dependent pathways.

Periodontal ligament (PDL) cells exhibit several osteoblastic traits and are parathyroid hormone (PTH)-responsive providing evidence for a role of these cells in dental hard-tissue repair. To examine the hypothesis that PDL cells respond to PTH stimulation with changes in proliferation and apoptotic signaling through independent but convergent signaling pathways, PDL cells were cultured from human bicuspids obtained from six patients. PDL cells at different states of maturation were challenged with PTH(1-34) intermittently for 0, 1, or 24 h/cycle or exposed continuously. Specific inhibitors to protein kinases A and C (PKA, PKC) and the mitogen-activated protein kinase cascade (MAPK) were employed. At harvest, the cell number, BrdU incorporation, and DNA fragmentation were determined by means of cell counting and immunoassays. Intermittent PTH(1-34) caused a significant increase in cell number in confluent cells as opposed to a reduction in pre-confluent cells. In confluent cells, the effect resulted from a significant increase in proliferation, whereas DNA fragmentation was reduced when PTH(1-34) was administered for 1 h/cycle but increased after PTH(1-34) for 24 h/cycle. Inhibition of PKC inhibited PTH(1-34)-induced proliferation but enhanced apoptosis. Inhibition of PKA enhanced proliferation and DNA fragmentation. Similar results were obtained in less mature cells, although, in the presence of the PKA inhibitor, the PTH(1-34)-induced changes were more pronounced than in confluent cells. In the presence of the MAPK inhibitor, all of the parameters examined were reduced significantly in both maturation states. Thus, PTH(1-34) mediates proliferative and apoptotic signaling in human PDL cells in a maturation-state-dependent manner via PKC-dependent and PKA-dependent pathways.

Adolescent↗

PubMed2006

[Hyperplasia of the coronoid process: diagnosis and treatment].

STUDY GOAL: As it is an unusual and infrequent clinical entity, hyperplasia of the coronoid process is often overlooked or diagnosed too late. The aim of this study was to characterize the morphology, etiology, and clinical picture of coronoid hyperplasia as well as to discuss its diagnosis and treatment. MATERIALS AND METHODS: All cases of histologically confirmed hyperplasia of the coronoid process treated in our center between 1995 and 2004 were analyzed. Patient data were evaluated with respect to age, gender, clinical symptoms, diagnostic work-up, and treatment. The extracted data were compared to those found in the literature. RESULTS: The study included 14 new cases and 101 cases already published: 96 with bilateral and 19 with unilateral hyperplasia. At the time of diagnosis, the subjects' mean age was 23.7 years. The patients in Bonn were all treated by coronoidectomy and appropriate physiotherapy. An improvement in mouth opening could be achieved in 86% of our patients. CONCLUSIONS: In comparison to the somewhat disappointing results of previously published studies with regard to mouth opening and mandibular mobility, our treatment concept seems to offer the possibility for improvement. Our study emphasizes the significance of three-dimensional CT techniques for diagnosis and surgical planning, the superiority of coronoidectomy over coronoidotomy, and the importance of dynamic physiotherapy to prevent postoperative scar formation.

Adult↗

PubMed2006

Some medicolegally important aspects of symphyseal injuries due to trauma.

A total of 58 cases of fatal trauma (forensic autopsies) were investigated for lesions of the pelvic girdle, the pubic symphysis, and for injuries distant from the pelvis. Traumata of the pubic symphysis were present in 30% (n = 17) of the cases. The symphyses were examined by x-ray and macroscopically related to the main violence (Abbreviated Injury Scale [AIS]). A correlation between the latter and the severity of the resulting injuries could be deducted. Characteristic patterns of symphyseal injuries included small hemorrhages, partial and complete ruptures, and also ruptures of the ligamentary insertions, which have not yet been described. The kind and severity of these lesions related to the intensity/direction of the violence are demonstrated and discussed.

Abbreviated Injury Scale↗

PubMed2006

Maturation-state dependent response of human periodontal ligament cells to an intermittent parathyroid hormone exposure in vitro.

BACKGROUND AND OBJECTIVES: Parathyroid hormone (parathyroid hormone) has been shown to be capable of exerting anabolic effects on bone when administered intermittently. We hypothesized that parathyroid hormone will modulate the response of periodontal ligament cells in terms of anabolic effects with respect to proliferation, differentiation and the production of key regulatory factors of bone remodeling such as osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) in a maturation-state dependent manner. METHODS: Periodontal ligament cells were cultured from human bicuspids obtained from six patients. Following characterization, confluent and preconfluent periodontal ligament cells were challenged with parathyroid hormone (1-34) for 0, 1, 3, 6 or 24 h within three incubation cycles of 48 h each. At harvest, the cell number, alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL production were determined by means of semiquantitative polymerase chain reaction (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast-like cells served as a reference. RESULTS: Intermittent parathyroid hormone treatment of confluent periodontal ligament cells caused a significant increase in proliferation (+32% maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin decreased at the transcriptional and translational level (-59.7% maximum). In preconfluent periodontal ligament cells, parathyroid hormone induced a decrease in proliferation (-66.3% maximum) but an increase in differentiation and osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and unaffected by parathyroid hormone treatment. Similar results were obtained in MG63 cells, whereas parathyroid hormone stimulation did not alter any of the parameters examined in dermal fibroblasts. CONCLUSION: These results indicate that human periodontal ligament cells respond to an intermittent parathyroid hormone exposure with changes in proliferation, differentiation and osteoprotegerin production in a maturation-state dependent manner and therefore might be regulatorily involved in periodontal regeneration.

Adolescent↗

PubMed2006

Parathyroid hormone modifies human periodontal ligament cell proliferation and survival in vitro.

BACKGROUND AND OBJECTIVE: Periodontal ligament (PDL) cells show traits that are typical of osteoblasts, such as osteoblastic marker gene expression and the ability to respond to parathyroid hormone (PTH) stimulation in an osteoblast-like manner with respect to differentiation and local factor production. In the present study, we hypothesized that human PDL cells might respond to PTH stimulation with changes in proliferation and cell survival and thereby provide another mechanism by which PTH might affect the reparative potential of PDL cells. We speculated that the maturation state of the cells and the mode of PTH(1-34) administration would have an impact on the cellular response. MATERIAL AND METHODS: PDL cells were challenged with PTH(1-34) intermittently or continuously at different maturation states. Cell number, 5-bromo-2-deoxyuridine (BrdU) incorporation, DNA fragmentation, nitric oxide production and the duration of the PTH(1-34) effect were determined. RESULTS: Intermittent PTH(1-34) treatment of preconfluent cells caused a significant increase in proliferation and DNA fragmentation, whereas in more mature cells, proliferation was less enhanced while apoptosis was more pronounced than in immature cells. Continuous PTH(1-34) exposure did not alter proliferation in any maturation state but increased DNA fragmentation in preconfluent cells. PTH(1-34) prevented etoposide-induced apoptosis after 6 h but no longer after 24 h. Nitric oxide production was unaffected. CONCLUSION: These results indicate that human PDL cells respond to PTH(1-34) with changes in proliferative and apoptotic signaling in a maturation-state-dependent manner. Besides changes in local factor production, these findings provide a further possible mechanism to support the idea that PDL cells possess the potential to be involved in the regulation of dental hard tissue repair.

Adolescent↗

PubMed2005

Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth.

The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. It is believed that this tissue contains stem cells and lineage committed progenitor cells or precursor cells (PCs) for cementoblasts, periodontal ligament cells, and osteoblasts. In this study, we report the isolation of PCs derived from dental follicle of human third molar teeth. These fibroblast-like, colony forming and plastic adherent cells expressed putative stem cell markers Notch-1 and Nestin. We compared gene expressions of PCs, human mesenchymal stem cells (hMSCs), periodontal ligament cells (PDL-cells) and osteoblasts (MG63) for delimitation of PCs. Interestingly, PCs expressed higher amounts of insulin-like growth factor-2 (IGF-2) transcripts than hMSCs. Differentiation capacity was demonstrated under in vitro conditions for PCs. Long-term cultures with dexamethasone produced compact calcified nodules or appeared as plain membrane structures of different dimensions consisting of a connective tissue like matrix encapsulated by a mesothelium-like cellular structure. PCs differentially express osteocalcin (OCN) and bone sialoprotein (BS) after transplantation in immunocompromised mice but without any sign of cementum or bone formation. Therefore, our results demonstrate that cultured PCs are unique undifferentiated lineage committed cells residing in the periodontium prior or during tooth eruption.

Adolescent↗

PubMed2005

In vitro differentiation of human dental follicle cells with dexamethasone and insulin.

The dental follicle is an ectomesenchymally derived connective tissue harboring precursor cells for the tooth supporting apparatus. In this study, we examined gene expression of freshly isolated human dental follicle cells during osteogenic differentiation in vitro. These plastic adherent fibroblastic cells express Notch-1, nestin and vimentin. We differentiated dental follicle cells with dexamethasone or insulin-based protocols into membrane-like structures containing mineralizing foci. An analysis of mineralized tissue with atomic force microscopy illustrated a bone and cementum-like structure. A real-time RT-PCR analysis was developed to investigate expression of typical osteoblast or cementoblast related genes during differentiation. Gene expressions of osteocalcin (OCN), bone morphogenic protein (BMP)-2 and nestin were increased during the both differentiation approaches. Our work demonstrates differentiation of dental follicle cells with an insulin-based protocol for the first time.

Adult↗

PubMed2005

PTH(1-34) affects osteoprotegerin production in human PDL cells in vitro.

Since periodontal ligament (PDL) cells exhibit several osteoblastic traits, we hypothesized that human PDL cells will respond to hormonal stimulation in an osteoblast-like manner. Confluent and pre-confluent PDL cells from six patients were challenged with PTH(1-34). Cell number, ALP, osteocalcin, osteoprotegerin, and RANKL expression were determined. Intermittent PTH(1-34) treatment of confluent PDL cells caused a significant increase in proliferation, whereas differentiation and osteoprotegerin production decreased significantly. In pre-confluent PDL cells, this treatment regimen induced a biphasic decrease in proliferation, but a biphasic increase in differentiation and osteoprotegerin production. Continuous PTH(1-34) exposure enhanced proliferation but inhibited osteocalcin production in confluent cells and stimulated osteoprotegerin production in pre-confluent PDL cells. RANKL was hardly detectable and unaffected by PTH(1-34) treatment. These results indicate that human PDL cells respond to PTH(1-34) in an osteoblast-like manner, and that the PTH(1-34) effect depends on the maturation state of the cells and on the mode of administration.

Adolescent↗

PubMed2005

Early responses of periodontal ligament cells to mechanical stimulus in vivo.

Previous studies have indicated that human periodontal ligament cells undergo osteoblastic differentiation via the ERK pathway under mechanical stress in vitro. This study aimed to verify this principle in vivo. The right upper first molars of 25 anesthetized rats were loaded with constant forces of 0.1 N for up to 8 hrs. The untreated contralateral side served as a control. Paraffin-embedded sections were analyzed by immunohistochemistry for proliferating cell nuclear antigen (PCNA), runt-related transcription factor 2 (Runx2/Cbfa1), and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2). In selected areas under tension, the proportions of Runx2-positive and pERK1/2-positive cells increased within 8 hrs of loading, whereas these proportions in selected areas under pressure were significantly lower than those in control teeth. Moreover, there were no significant changes in the number of PCNA-positive cells. Thus, mechanical stimulus up-regulates Runx2, and this regulation may be achieved via the ERK pathway.

Animals↗

PubMed2005

Distribution of components of the insulin-like growth factor system in the temporomandibular joint of the aging mouse.

The temporomandibular joint (TMJ) is a exceptional joint involved in growth as well as mastication. In adult mice, it provides a model for age related natural osteoarthritis (OA). The insulin-like growth factor (IGF-) system plays was tested because it plays important roles in cartilage biology and OA pathogenesis. Decalcified and paraffin embedded TMJs of 48 NMRI mice sacrificed in groups of three male and females each at the ages of 3, 4, 5, 7, 9, 10, 12, and 18 months were prepared for histopathology and immunohistochemistry for IGF-I and -II, IGF1 receptor and IGF binding proteins -1, -2, -3, -4, -5, and -6. Histopathological signs of OA were obvious in the TMJ of all animals older than 5 months, but did not show a clear age-related staging. Immunoreactivity for all IGF components was found in unchanged anterior and posterior regions of the condyle and in regions of advanced OA lesions. Receptor immunostaining was obvious in all ages. Most IGFBPs showed immunostaining patterns similar to IGFs. While the anterior and posterior zones of the condylar cartilage appear to be specialized judging by structure and IGF immunostaining pattern, probably due to metabolic or biomechanical peculiarities, the central portion undergoes early degeneration. In advanced OA stages, the IGF system seems to be upregulated to induce repair processes. According to their mainly inhibiting functions, IGFBPs may suppress anabolic IGF activities.

Aging↗

PubMed2003

Osteotomy with 80-micros CO2 laser pulses--histological results.

Haemostatic and aseptic effects and intricate cut geometry are beneficial aspects of non-contact laser osteotomy. Collateral thermal damage, however, has severely limited the use of conventional lasers. The purpose of this study was to test the side effects on bone after cutting it with short CO2 laser pulses and simultaneous application of a fine air-water spray. The 10.6 microm CO2 laser emitted 80 micros pulses of 46 mJ energy, f=100 Hz, focused to a spot diameter of 130 ìm. Scan rate amounted to 40 mm/s. To approximate live conditions 10 samples of cortical bone and 10 rib segments were prepared immediately after sacrificing of pigs. A reference cut with a bandsaw and three laser cuts with an increasing number of beam passes (4, 16, 64) were performed on each sample. Half of the samples were decalcified in EDTA. The others were embedded in plastic to cut non-decalcified sections. The laser incisions were not accompanied by carbonisation. The incisions with slightly convergent walls were 150 ìm wide. The depths of the cavities increased with the number of the beam passes from approximately 0.5 mm (4 passes) to 3 mm (64 passes). At the border of the incisions two narrow zones of damage were noted: an amorphous intensively stained zone of 1-3 microm width and a wider, also sharply demarcated but faintly stained zone of 7-10 microm. A broader zone of about 50 microm was characterised by empty lacunae and osteocyte damage. These effects were not predictable; intact osteocytes were also observed near to the cut surface. Polarised light microscopy showed no alterations in the inorganic structure of the bone at the cut borders. The histological results indicated only minimal damage to bone ablated at the specified parameters. The described laser procedure might have advantages over mechanical instruments.

Animals↗

PubMed2003

[Numerical study of tension and strain distribution around rat molars].

A knowledge of the mechanical processes triggered in the bone and periodontal ligament (PDL) by orthodontic forces applied to a tooth is of decisive importance for an understanding of the subsequent remodelling around the tooth. To investigate these mechanical relationships, three-dimensional finite element (FE) models of the first lower molar in the rat were established. On the basis of digitized serial histological sections, these FE models were generated semi-automatically. Using various simplified geometrical variations, an appropriate FE model for the analysis of the stress and strain distributions was established. The numerical analyses were carried out under a mesially directed force of 0.1 N. Stress distributions in the bone and PDL showed a similar pattern, while strains in the bone were lower than in the PDL by a factor of 10-5. The data confirm the assumption that strain patterns in the PDL may be the key stimulus of bone remodelling.

Animals↗

PubMed2002

Localization of IL-1alpha, IL-1 RI, TNF, TNF-RI and TNF-RII during physiological drift of rat molar teeth--an immunohistochemical and in situ hybridization study.

Proinflammatory cytokines such as IL-1 and TNF play a crucial role in the initiation of an inflammatory response to bacterial irritants and subsequent periodontal tissue destruction. The object of the present investigation was to examine the possible role of these cytokines in the periodontal tissues under physiological conditions. To this end we studied the expression of IL-1alpha and TNF both at the transcription and protein level by means of in situ hybridization and immunohistochemistry and investigated the distribution of IL-1RI, TNF-RI and TNF-RII immunohistochemically in 10 jaw specimens taken from male Wistar rats. We found IL-1alpha and TNF mRNA to be focally transcribed in bone marrow cells of the monocyte/macrophage lineage, in gingival epithelium as well as in single osteoblasts and osteoclasts. Additionally, IL-1alpha mRNA was detected in PDL-fibroblasts and epithelial remnants of Malassez. The IL-1alpha immunohistochemistry observations were corroborated by the in situ hybridization results. TNF and its receptors were not detected at the protein level. These data suggest that IL-1alpha and its receptor are of some importance in the maintenance of tissue homeostasis and remodeling events accompanied by physiological tooth movement.

Animals↗

PubMed2002

Immunohistochemical localization of receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) in human deciduous teeth.

Osteoblasts and osteoclasts are involved in bone formation and resorption. RANK and RANKL [receptor activator of nuclear factor kappaB (ligand)], two cytokine-like proteins of the tumor necrosis factor superfamily, are localized on these bone cells and are crucial for the regulation of osteoclastic cell differentiation from hematopoietic precursors and also for the upregulation of mature osteoclasts mediated by cell-to-cell contact and a subsequent cascade of diverse intracellular signaling processes in the osteoclasts. It was the aim of this study to examine the sites of expression of RANKL and RANK in the corresponding cells of human dental hard and periodontal tissues using immunohistochemical light microscopical methods on tissue sections of 15 paraffin-embedded human deciduous teeth undergoing root resorption. We detected granular cytoplasmic RANKL-immunoreactivity in odontoblasts, pulp fibroblasts, periodontal ligament fibroblasts, and in single odontoclasts, the latter finding suggesting an autocrine/paracrine role. RANK-positive cells were identified as multinucleated odontoclasts localized near the dentine surface in resorption lacunae or as mononucleated precursors. These findings indicate that human dental cells express key mediators of hard tissue resorption and, though the RANK/RANKL-system may not be the sole regulator of tooth root resorption, these factors could at least contribute to this complex process under both physiological and pathological conditions.

Adsorption↗

PubMed2001

[Immunohistochemical localization of insulin-like-growth-factor-binding protein 6 in the head area of the mouse].

BACKGROUND: The insulin-like growth factor (IGF) system is an important regulator of cell growth and differentiation. The mitogenic and metabolic activities of IGFs are modulated by a family of six high-affinity IFG binding proteins (IGFBPs). IGFBP-6 is unique among the IGFBPs in its preferential binding of IGF II. METHODS: In this study, specific antibodies against recombinant mouse IGFBP-6 generated in chicken were used to localize IGFBP-6 by immunohistochemistry in the head region during late embryonic and newborn mice. RESULTS: Immunoreactivity was detected in oral and nasal mucosa, tooth-forming anlage, anlage of skeletal muscle, anlage of submandibular glands, enchondral ossification, and osteoclasts.

Animals↗

PubMed2001

Immunohistochemical detection of components of the insulin-like growth factor system during skeletal muscle growth in the pig.

The insulin-like growth factor (IGF) system plays an important role in postnatal somatic and skeletal muscle growth in pigs. There is little information on the occurrence and distribution of components of the IGF system in postnatal porcine skeletal muscle. IGF-I, IGF receptor 1 (IGF1R) and the IGF-binding proteins IGFBP-1 and -3 in longissimus dorsi and triceps brachii were localized in muscle biopsies from 12 commercially crossbred pigs aged from 28 to 199 days as well as from the sire generation, by immunohistochemistry. Plasma IGF-I concentrations were also determined using radio-immunoassays. Unlike other species, IGF-I was localized in porcine skeletal muscle fibres. Staining intensity correlated with the highest plasma IGF-I levels and phases of intensive muscle growth from the 11th to 22nd week. The pattern of IGF1R immunostaining, which was strong, correlated with that of IGF-I, IGF1R was also localized in endomysial tissues. IGFBP-1 was not detected within muscle fibres, but was found in the endomysium and vessel walls, while IGFBP-3 was localized with IGF-1 and its receptor. Higher magnification revealed that IGF1R, IGFBP-3 and probably IGF-I appeared in the tubular system. Inhibitory as well as stimulating controls of IGFBP-1 and -3 on IGF functions are discussed, which may maintain a balance between autocrine growth promoting activities of IGF-I and IGF1R.

Aging↗

PubMed2001

Glycoconjugate distribution in early human notochord and axial mesenchyme.

Glycosylation patterns of cells and tissues give insights into spatially and temporally regulated developmental processes and can be detected histochemically using plant lectins with specific affinities for sugar moieties. The early development of the vertebral column in man is a process which has never been investigated by lectin histochemistry. Therefore, we studied binding of several lectins (AIA, Con A, GSA II, LFA, LTA, PNA, RCA I, SBA, SNA, WGA) in formaldehyde-fixed sections of the axial mesenchyme of 5 human embryos in Carnegie stages 12-15. During these developmental stages, an unsegmented mesenchyme covers the notochord. Staining patterns did not show striking temporal variations except for SBA which stained the cranial axial mesenchyme only in the early stage 12 embryo and for PNA, of which the staining intensity in the mesenchyme decreased with age. The notochord appeared as a highly glycosylated tissue. Carbohydrates detected may correspond to adhesion molecules or to secreted substances like proteoglycans or proteins which could play an inductive role, for example, for the neural tube. The axial perinotochordal unsegmented mesenchyme showed strong PNA binding. Therefore, its function as a PNA-positive "barrier" tissue is discussed. The endoderm of the primitive gut showed a lectin-binding pattern that was similar to that of the notochord, which may correlate with interactions between these tissues during earlier developmental stages.

Cell Membrane↗

PubMed2001

Botulinum toxin type A induces apoptosis in nasal glands of guinea pigs.

Nasal hypersecretion is predominantly caused by overaction of nasal glands, which are mainly under cholinergic control. In this work, we investigated the influence of botulinum toxin A (BTA) on the nasal mucosal tissue of the maxillary sinus turbinates of guinea pigs (n = 10) that were painlessly sacrificed 10 days (short-term group) or 3 months (long-term group) after local treatment with 20 units of BTA (Botox) or 0.2 mL of 0.9% sodium chloride (control). Histologic investigation of the nasal mucosal tissue of the BTA-treated animals (short-term group) showed degeneration of glands and ducts and apoptotic nuclei on TUNEL staining of these structures. The control animals revealed normal glandular tissue and no apoptosis. The animals of the long-term group showed almost normal glandular tissue and only a few apoptotic nuclei. In conclusion, BTA induces temporary apoptosis in the nasal glandular compartment of guinea pigs.

Animals↗