Proliferation and Differentiation of Cultured Human Keratinocytes Is Modulated by 1,25-Dihydroxyvitamin D3 and Synthetic Vitamin D3 Analogues in a Cell Density-, Calcium-, and Serum-Dependent Manner

The study investigated how culture conditions affect the sensitivity of human keratinocytes to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and synthetic vitamin D3 analogues. It was found that keratinocyte proliferation and differentiation responses varied based on cell density, calcium concentration, and serum presence. At 50-60% confluence in serum-free medium with 0.09 mM Ca2+, vitamin D3 analogues had minimal impact on proliferation and differentiation. However, at 30% confluence, 1,25(OH)2D3 significantly inhibited proliferation, an effect enhanced by 3% charcoal-stripped fetal calf serum. Increasing Ca2+ to 0.3 mM stimulated differentiation and showed a biphasic effect on proliferation. Sensitivity to synthetic analogues was higher than to 1,25(OH)2D3, with differentiation occurring at concentrations 10-30 times lower than for proliferation. The study concluded that keratinocyte response to vitamin D3 analogues is influenced by cell density, serum, and calcium levels.