Abstract for presentation at 13th International Congress on Oral Pathology and Medicine

Differentiation of oral epithelium is regulated by GM-CSF and KGF at early but not terminal stages

  • Daniela Costea, University of Bergen, Norway
  • Keerthi Kulasekara, University of Bergen, Norway
  • Evelyn Neppelberg, University of Bergen, Norway
  • Gunnvor Øijordsbakken, University of Bergen, Norway
  • Olav Vintermyr, University of Bergen, Norway
  • Christine Johannessen, University of Bergen, Norway

    • Previous studies have shown that fibroblasts have a crucial role on in vitro oral epithelial differentiation, but the responsible factors have not yet been identified. In this study a number of fibroblast-derived factors were tested with respect to their role on oral epithelial differentiation. Organotypic cultures of normal human oral mucosa were constructed from primary normal human oral keratinocytes grown on top of type I collagen gels with or without fibroblasts. The cultured tissues were assessed by histomorphometry, immunohistochemistry, and the TUNEL method. Oral epithelium grown on simple collagen gels in absence of fibroblasts had an undifferentiated phenotype with (1) weak, scattered expression of cytokeratin (CK) 13, (2) expression of EGF-R and integrins throughout all cell layers, (3) no deposition of collagen IV, and (4) TUNEL positive cells randomly distributed within the epithelium. Addition of KGF (10ng/ml) did not change the undifferentiated phenotype of the oral epithelium grown on simple collagen gels. Addition of GM-CSF (10ng/ml) induced the expression of CK 13 in all suprabasal cell layers only. The admixture of GM-CSF and KGF induced, in addition, polarization of EGF-R and integrins to the basal cell layer, and deposition of collagen IV. There was no polarization of the TUNEL positive cells to the superficial layer, suggesting that cells did not complete their terminal differentiation in these cultures. Polarization of TUNEL positive cells to the superficial cell layer (terminally differentiated cells) occurred, in addition to all the others markers of differentiation tested, only in the presence of fibroblasts in the collagen gels either in direct contact or at distance from keratinocytes (sandwich models). These data indicate that major aspects of oral epithelial differentiation are regulated by the synergic combination of GM-CSF and KGF, but its terminal stage is controlled by another yet unidentified fibroblast-derived diffusible factor.

    Conference Organiser - ICMS Pty Ltd