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  • Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy.

Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy.

Archives of dermatological research (2014-07-17)
Hanne Norsgaard, Sandrine Kurdykowski, Pascal Descargues, Tatiana Gonzalez, Troels Marstrand, Georg Dünstl, Mads Røpke
ABSTRACT

The calcipotriol/betamethasone dipropionate fixed-combination gel is widely used for topical treatment of psoriasis vulgaris. It has been hypothesized that calcipotriol counteracts glucocorticoid-induced skin atrophy which is associated with changes in the extracellular matrix (ECM). To elucidate the combined effects of calcipotriol and betamethasone on key ECM components, a comparative study to the respective mono-treatments was carried out. The effect on collagen I synthesis, matrix metalloproteinase (MMP) secretion, and hyaluronic acid (HA) production was investigated in primary human fibroblast and keratinocyte cultures as well as in a human skin explant model. We show that calcipotriol counteracts betamethasone-induced suppression of collagen I synthesis. Similarly, calcipotriol and betamethasone have opposing effects on MMP expression in both fibroblasts and keratinocytes. Moreover, calcipotriol is able to restore betamethasone-impaired HA synthesis in keratinocytes and prevent betamethasone-induced epidermal thinning in minipigs upon treatment with the calcipotriol/betamethasone gel. In summary, our results show for the first time in primary human skin cultures that calcipotriol reduces early signs of betamethasone-induced skin atrophy by modulation of key ECM components. These results indicate that the calcipotriol component of the fixed-combination gel counteracts the atrophogenic effects of betamethasone on the skin.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DAPI, for nucleic acid staining
Betamethasone dipropionate, European Pharmacopoeia (EP) Reference Standard
USP
Betamethasone dipropionate, United States Pharmacopeia (USP) Reference Standard
Supelco
Betamethasone Dipropionate, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Anti-Procollagen Type I Antibody, NT, clone M-58, culture supernatant, clone M-58, Chemicon®
Sigma-Aldrich
Monoclonal Anti-HAS1 antibody produced in mouse, clone 3E10, ascites fluid