Effect of 1 alpha,25-dihydroxyvitamin D3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions

Abstract

The effect of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2-D3] on the proliferation and morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown under defined, serum-free conditions was studied. 1 alpha,25-(OH)2-D3 caused a dose-dependent decrease in proliferation and an increase in the morphologic differentiation of human cultured keratinocytes. The number of attached basal cells decreased when exposed to 1 alpha,25-(OH)2-D3, whereas the number of attached squamous cells, terminally differentiated desquamated cells, and cornified cells increased concurrently. In addition, after incubation with 1 alpha,25-(OH)2-D3, there was a shift to cells of lighter density. In conjunction with its effect on the basal cells, 1 alpha,25-(OH)2-D3 resulted in an inhibition of DNA synthesis. The activity of transglutaminase, the enzyme responsible for cross-linking the proteins of the cornified envelope, was stimulated by 156% with 1 alpha,25-(OH)2-D3, but not with 1 beta,25-(OH)2-D3, a biologically inert isomer. Therefore it appears that 1 alpha,25-(OH)2-D3 is a potent inhibitor of keratinocyte proliferation as well as a stimulator of epidermal terminal differentiation.