Craniofacial biology gene expression during tooth

development.
Supervisor:
Cosupervisors:

ProfessorHaraldOsmundsen
ProfessorSteinarRisnes
PhDfellowMariaA.Landin
PhDfellowAmerSehic

Tooth development results from interactions between oral epithelium and adjacent
mesenchyme. More than 2000 genes are likely involved during odontogenesis. So far
expression of about 250 genes and/or translated proteins has been detected. The main events
during tooth development involve dentition patterning, establishment of tooth morphology,
differentiation of mesenchymal cells into dentin-producing odontoblasts and epithelial cells
into enamel-producing ameloblasts. For this to occur the coordinated operation of several
fundamental biological processes (e.g. developmental timing, cell fate, proliferation,
apoptosis, cellular growth and morphogenesis) are required. How, this is achieved by use of
genes and gene-products are the ultimate object of the study.
Mouse is used as experimental animal, using both wild-type mice and relevant knockout mice. Molar tooth germs can be isolated at various times during development, both at the
foetal stage and after birth. Gene expression is monitored using microarrays, real-time RTPCR and in situ hybridisation. An essential feature of this work entails the use of
bioinformatics to suggest how changes in genes expression may influence cellular physiology.

Craniofacial biology epigenetic regulation of gene

expression during development of oral tissues
Supervisor:
Cosupervisors:

ProfessorHaraldOsmundsen
PhDfellowAnneMartheJevnaker
AssociateprofessorHildeGaltung

Very recently it has been established that non-coding RNA may be important posttranscriptional regulators of gene expression. MicroRNAs (miRNAs) are one class of such
regulators. The function of miRNAs during development of oral tissues is poorly studied. This
project therefore aims to study the expression of miRNAs during development of the murine
molar tooth germ and submandibular salivary gland.
Using mouse as experimental animal tooth germs and salivary glands are isolated at
various stages during development for profiling of miRNAs. MiRNAs are measured by
microarray hybridisation of by real-time PCR. Experimental data are interpreted using
bioinformatics software which provides statistical significant associations between miRNA
profiles and cellular physiology. Further information regarding involvement of miRNAs
during tissue differentiation can be obtained by extending these studies using relevant knockout mice.

The role of adipokines and cranial development

Supervisors: AssociateprofessorJanneReseland,Instituttforkliniskodontologi
ProfessorStlePetterLyngstadaas,Instituttforkliniskodontologi,UiO

During skeletal development, condensation of multipotential mesenchymal cells to

differentiate towards the various cell types is an important process. One such process is the
formation of chondrocytes from undifferentiated mesenchymal cells. The molecular
mechanisms, however, are not well understood. Cells of mesenchymal origin share many
characteristics in gene expression during differentiation and even though their phenotypes
may differ markedly, mature adipocytes, chondrocytes and osteoblasts express and secret
several common factors that underline the close relationship between these cells.
We have previously demonstrated the expression of the adipokines leptin, adiponectin and
resistin in bone forming cells. Although recombinant adipokines stimulated osteoblast
proliferation, their role in bone metabolism remains unknown. Adipokines may, by binding to
its receptors, directly influence the metabolism of cells in bone. Leptin appears to stimulate
osteoblast differentiation, whereas resistin recruit stem cells to differentiate in both
osteoblastic and osteoclastic direction. Adiponectin is structural similar to TNF-, RANKL
and osteoprotegerin, which all are involved in osteoclastogenesis. We have found that
Adiponectin regulates the TNF--induced nuclear transcription factor-B activation, the
signaling pathway of RANKL. OPG, RANK, and RANKL do also play a role in early tooth
development, and there is a known relationship between RANKL in dentary bone
mesenchymal cells and RANK and OPG in tooth germ.
High expressions of adiponectin has been found in Meckels cartilage, as well as in cartilage of
the developing osoccipital and jaw of the developing vertebra (neck) in 18 days intra-uterine
rat embryo. We have also identified adiponectin in mandibular and jaw bone. The developing
root of alveolar bone in 19 days old rats, as well as the periosteum of 10 days old rats were
highly positive for adiponectin.
Practical approach:
(1) Characterize the expression and regulation of adiponectin in osteoblasts, odontoblasts and
ameloblasts.
(2) Study the paracrine and endocrine role of adiponectin in matrix maturation and
mineralization.
(3) Study the effect of adiponectin on tooth development and bone growth in a rodent
craniofacial model.