Premium
Granulocyte macrophage‐colony stimulating factor and keratinocyte growth factor control of early stages of differentiation of oral epithelium
Author(s) -
Das Ridhima,
Virlan Maria Justina Roxana,
Xenaki Victoria,
Kulasekara Keerthi K.,
Lukandu Ochiba,
Neppelberg Evelyn,
Vintermyr Olav K.,
Johannessen Anne. Chr.,
Calenic Bogdan,
Costea Daniela Elena
Publication year - 2022
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12867
Subject(s) - keratinocyte growth factor , epidermal growth factor , keratinocyte , microbiology and biotechnology , biology , fibroblast , fibroblast growth factor , epithelium , growth factor , fibroblast growth factor receptor 3 , cellular differentiation , basic fibroblast growth factor , immunology , chemistry , pathology , medicine , receptor , in vitro , biochemistry , gene
Abstract Oral epithelial differentiation is known to be directed by underlying fibroblasts, but the responsible factor(s) have not been identified. We aimed here to identify fibroblast‐derived factors responsible for oral epithelial differentiation. Primary normal human oral keratinocytes and fibroblasts were isolated from healthy volunteers after informed consent ( n = 5) and 3D‐organotypic (3D‐OT) cultures were constructed. Various growth factors were added at a range of 0.1‐100 ng/ml. 3D‐OTs were harvested after ten days and assessed histologically, by immunohistochemistry and the TUNEL method. Epithelium developed in 3D‐OT without fibroblasts showed an undifferentiated phenotype. Addition of granulocyte macrophage‐colony stimulating factor (GM‐CSF) induced expression of cytokeratin 13 in suprabasal cell layers. Admixture of GM‐CSF and keratinocyte growth factor (KGF) induced, in addition, polarization of epidermal growth factor (EGF) receptor and β1‐integrin to basal cell layer and collagen IV deposition. Terminal differentiation with polarization of TUNEL‐positive cells to superficial layers occurred only in the presence of fibroblasts in collagen gels either in direct contact or at distance from normal oral keratinocytes. Taken together, these results show that major aspects of oral epithelial differentiation are regulated by the synergic combination of GM‐CSF and KGF. However, the terminal stage seems to be controlled by other yet unidentified fibroblast‐derived diffusible factor(s).