Effects of calcipotriol(MC 903), a novel synthetic derivative of vitamin D3 on the growth of cultured human keratinocytes and melanocytes

Hong, Dae Kwang; Yoon, Tae Jin; Kim, Nack In; Park, Jai Kyung; Haw, Choong Rim

Abstract

The cutaneous synthesis of vitamin D in response to ultraviolet radiation exposure is the most important factor in maintaining vitamin D balance in Man. The skin is not only the site of vitamin D synthesis, but also a target organ for calcitriol(1, 25-dihydroxy-vitamin D) which is naturally occuriag, hormonally active form of vitamin E. It is now known that calcitriol inhibits the proliferation of epidermal cells and induces her differentiation. In this study, epidermal keratinocytes and melanocytes were isilated from the neonatal foreskin, and were culturod using a MCDB 153 and modified TIC media, respectively. And then various concentratioris of calcipotriol(MC 903), a synthetic aralogue of calcitriol, were added to each culture. The effects of calcipotriol on the growth of human keratinocytes and melanocytes were investigated. The results were as follows : 1. The addition of calopotriol to human keratinocyte and melalocyte cultures inhibited their proliferation in a dosdependent manner. 2. Calcipotriol had no effects on the melanization process of the melanocyte. 3. Calcipotriol was found to inhibit the proliferation, however it induced the terminal differentiation of cultured keratinocytes, as judged by morphologicai changes. The decreased density of kerationcytes, The formation of cornified cells, and the cellular destruction in a concentration of 10 M of calcipotriol were observed. 4. By using the light atid the electron microscope, we observed that the epidermal thickness was decreased and terminal differentiation was facilitateir. Living Skin Equivalent (LSE) according to the increasing concentration of calcipotriol. A]i)parent cytotoxic effects were observed in 10 M, 10 M of calcipotriol. In summary, the above results indicate that the addition of calcipotriol to the in vitro culture system of human keratinocyte and melanocyte induces the biologic process of terminal differentiation of keratinocytes and inhibits proliferation of keratinoytes and melanocytes in a dose-dependent manner.