Overview of projects which have been done in the past years:
Gene expression in salivary glands of Sjögren´s syndrome
The aim of this study was to identify genes that were differentially expressed in the salivary glands of patients with primary Sjögren´s syndrome compared to healthy controls, as well as in an experimental Sjögren´s syndrome mouse model, in order to elicit the genes involved and the pathways activated in the salivary glands of both human and mice with a Sjögren syndrome like disease. Furthermore, a mapping of the salivary gland proteome and identification of differentially expressed proteins in the salivary glands of primary Sjögren´s syndrome was conducted.
Interestingly, a distinct difference in gene expression levels of the minor salivary glands were found, enabling a simple class prediction method to correctly classify19 of 20 samples as either patient or control, based on the top 5 differentially expressed genes.
Collaborators:
Professor Anne Isine Bolstad, Department of Clinical Dentistry - Periodontics
Professor Roland Jonsson, Broegelmanns Research Laboratory, The Gade Institute,
Trond Ove R. Hjelmervik, PhD
Genetic studies of Fc gamma receptors in Sjögren´s syndrome
FcΥ receptors are glycoproteins that bind the Fc region on IgG. Genetic variations in the low-affinity receptors have been associated with different diseases. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in FcΥR can contribute to interindividual differences and differences in gene expression. For instance has CNVs in the FCGR3B gene been associated with glomerulonephritis in systemic lupus erythematosus (SLE) and with increased susceptibility to other autoimmune diseases. The project aims at investigating polymorphisms and CNV in genes encoding the FcΥ receptors in patients with Sjögren´s syndrome.
Collaborators:
Professor Anne Isine Bolstad, Department of Clinical Dentistry- Periodontics,
Professor Johan G. Brun, Institute of Medicine, Section for Rheumatology,
Dr. Silke Appel, Broegelmann Research Laboratory, The Gade Institute.
PhD fellow: Karstein Haldorsen, MD.
Etiopathogenesis of periodontal disease – searching for disease markers
Periodontitis is one of the most common infections in man. It is initiated by oral microorganisms colonizing the tooth surface in the dentogingival region entailing inflammation in the supporting tissue of the tooth. If the inflammation is left untreated, destruction of the surrounding tissue and tooth loss may be the consequence.
Periodontal disease is a multifactorial disease, the development of which is dependent on the virulence of the microorganisms, the immune response of the host, genetic factors, and environmental factors such as smoking.
During the last decades, research on disease mechanisms and pathogenesis on a molecular level has been in focus. In spite of this, disease etiology and pathogenesis is still not clear.
By the projects in this group, we aim at gaining increased knowledge of how periodontal disease develops on a molecular level in order to improve periodontal disease diagnostics, treatment and prevention in the future. There is a special interest in identifying disease markers. The experiments are performed on biological material from patients with periodontal disease.
One of the projects which is ongoing includes patients with aggressive periodontal disease. This is a form of periodontal disease where there is a rapid destruction of the periodontal attachment apparatus, often in young patients.
People:
Professor Anne Isine Bolstad (Principal Investigator), Department of Clinical Dentistry - Periodontics,
Post doc Manal Mustafa, Department of Clinical Dentistry - Periodontics.
PhD fellow Hager Zein Alabdeen, Department of Clinical Dentistry - Periodontics
There are also international collaborators in the project.
Etiopathogenesis in periodontal disease – Studies on integrins in the periodontal ligament
Cells in tissue interact with other cells and with proteins in the extracellular matrix via specific receptors called integrins. Integrins have an important function in binding cells to the surrounding tissue, and are important actors in the transfer of signals from the surroundings into the cell. Integrins also have an important role in embryonic development and wound healing.
In this project, the repertoire of integrins in the periodontal ligament was determined on RNA and protein levels. Most interest was dedicated to the collagenbinding integrins, with special emphasize on the function of the α11β1 integrin. Integrin α11β1 in the periodontal ligamnet is involved in tooth eruption of mouse incisors. No polymorphisms were identified in the promoter region of DNA from patients with chronic periodontal disease.
More information of the projects can be found here:
https://www.uib.no/rg/matrix
Collaborators:
Professor Anne Isine Bolstad, Department of Clinical Dentistry - Periodontics
Professor Donald Gullberg, Department of Biomedicine - Section of Physiology.
Post Doc Malgorzata M. Barczyk, PhD, Department of Biomedicine - Section of Physiology.
The project is supported by L. Meltzers høyskolefond
The Lymphotoxin-beta receptor (LTBR) signaling pathway studied in Sjögren´s syndrome like disease in NOD mice
Sjögren's syndrome is characterized by dry eyes and dry mouth due to reduced tear and saliva secretion. Although extensive research has been conducted on the disease, its mechanisms are still not fully understood, and treatment is therefore only symptomatic. There is also a lack of simple, specific diagnostic tests.
It has been documented that the interaction between LTBR and lymphotoxin αβ plays a key role in the formation and maintenance of secondary lymphoid structures. Secondary lymphoid structures are also formed in the salivary glands of patients with Sjögren's syndrome. Since LTB was among the most highly expressed genes in the salivary glands of patients with Sjögren's syndrome compared to healthy individuals in microarray experiments (Hjelmervik et al., 2005), we wanted to investigate the significance of the LTBR signaling pathway in more detail.
In a mouse model of Sjögren’s syndrome-like disease, it was investigated whether blocking the signaling pathway with an LTBR antagonist could prevent development or reduce the size of inflammatory infiltrates in the salivary and lacrimal glands. The results show that B-cell and T-cell infiltrates in the salivary glands were significantly reduced. Lymphoid neogenesis was also inhibited by the treatment, and there was a partial restoration of saliva secretion.
Several ongoing studies aim to explore this in greater detail.
Project Manager: Professor Anne Isine Bolstad, Department of Clinical Dentistry – Periodontology
Collaborators:
Professor Kathrine Skarstein, Gade Institute – Section for Pathology
The project also has international collaborators.
The project is supported by Helse Vest.
Regulating mechanisms in teeth
Signal substances regulate normal functions and defence mechanisms and repair following tissue injury. The aim of the research is to increase knowledge about mechanisms that control the outcome of injuries in teeth. Teeth in function are normally subjected to external forces, disease and damage, resulting in inflammatory changes in teeth and supporting tissues. Pain, both of chronic and acute character, is often an unwanted side-effect. As teeth are extremely well supplied with nerve fibres, teeth represent an excellent model system to study how nerve tissue is affected by injury and inflammation, and also the effects of nerve tissue on the outcome of tissue injury. By functional studies, inner steering mechanisms that sustain balance in these tissues are investigates. Clinical studies are included in the project.
People:
Professor Inge Fristad, DDS, PhD, Department of Clinical Dentistry - Endodontics, University of Bergen
Professor Ellen Berggreen, DDS, PhD, Department of Biomedicine - Physiology, University of Bergen
Assoc. Prof. Athansia Bletsa, DDS, PhD, Department of Clinical Dentistry - Endodontics, University of Bergen
Lymphangiogenesis during development of apical periodontitis
Apical periodontitis is a common inflammatory disease that dentists either prevent or treat when they give patients a root canal treatment. This condition is caused by bacteria in the root canal system of the tooth and is characterized by inflammatory reaction around the root tip with concomitant bone resorption.
This project would like to investigate the role of various inflammatory mediators during disease development with main focus on vascular endothelial growth factors (VEGFs). These factors are closely related to vasculogenesis, namely blood and lymphatic vessels' growth but their involvement in apical periodontitis and inflammatory bone resorption has not yet been investigated.
In this project, animal (rat/mouse) models of apical periodontitis, as well as biopsies from patients with apical periodontitis will be used.
People:
Professor Ellen Berggreen, Department of Biomedicine - Physiology, University of Bergen
Associate Professor Nancy Bletsa, Department of Clinical Dentristry-Endodontics and Department of Biomedicine, University of Bergen
PhD candidate Anca Virtej, Department of Biomedicine - Physiology, University of Bergen
Orthodontically induced root and alveolar bone resorption: Inhibitory effect of systemic doxycycline administration in rats
The aim of this study was to investigate the effect of systemic administration of low dose doxyclycline (DC) on orthodontic root resorption. The effect on alveolar bone, the cell population involved, and the amount of tooth movement were also evaluated.
Orthodontically induced root resorption was performed in rats, by exerting 50 g force on maxillary first molars for 7 – 14 days. Half of the animals (28 rats) received systemic administration of DC before insertion of the orthodontic appliance. The compressed areas at the mesial aspect of the distopalatal roots were histomorphometrically evaluated. The results revealed a significant less root resorption in rats with DC administration. The number of TRAP-positive cells (odontoclasts, osteoclasts, giant cells) was significantly reduced as compared to non-DC administrated group. In conclusion, systemic administration of low-dose DC in rats may have an inhibitory effect on orthodontically induced resorptive activity.
People:
Pongsri Brudvik, Professor, DDS, Lic.odont, PhD, Department of Clinical Dentistry – Orthodontics, University of Bergen
Polbhat Tripuwabhrut, PhD candidate, DDS, Department of Clinical Dentistry – Center for Dental Clinical Research, University of Bergen
What causes missing teeth?
Missing permanent teeth is a common problem (ca 7%) in the Norwegian population. The mechanisms behind failing tooth formation are not known, but most of these deviations seem to be familiar. Some families experience severe problems and need of treatment. Department of Clinical Dentistry and Department of Biomedicine collaborate in search for mechanisms behind failing tooth development. The future goal is to improve treatment for this group of patients. The investigations are based both on clinical and molecular biology methods.
People:
Assoc. Prof. Marit Midtbø, DDS, PhD, Department of Clinical Dentistry - Orthodontics, Faculty of Medicine and Dentistry, University of Bergen
Professor Keijo Luukko, DDS, PhD, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen
Professor Päivi Kettunen, DDS, PhD, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen