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Effects of 1α,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs

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Abstract

In the human hair follicle, outer root sheath (ORS) cells constitutively express the hyperproliferation-associated keratins 6, 16 and 17 instead of keratins 1 and 10 found in interfollicular epidermis. In organotypic cultures, ORS cells form a stratified epithelium which in many respects resembles psoriatic skin: it has a hyperplastic tissue architecture and a poorly developed granular layer, and expresses hyperproliferation-associated keratins. Therefore, we studied the effects of the antipsoriatic compounds 1α,25-dihydroxy-vitamin D3 (1α,25-(OH)2-D3) and its synthetic derivative calcipotriol on cultured ORS cells. In monolayer cultures, 10−6 M 1α,25-(OH)2-D3 or calcipotriol completely blocked ORS cell proliferation. This inhibitory effect was substantially reduced at 10−8 M. Incubation of organotypic ORS cultures with both vitamin D analogues resulted in a marked thinning of the living cell compartment concomitant with a thickening of the horny layer. A reduced expression of differentiation markers such as keratins 10,16 and 17, involucrin and filaggrin paralleled the thinning of the stratum Malpighi. As determined by quantification of BrdU-positive cells, ORS cell proliferation was apparently not affected by the vitamin D analogues, indicating that these compounds mainly operate by accelerating the differentiation pathway within the suprabasal living cell compartment. No alteration in the expression of the α6- and Β1-integrin chains was found.

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  1. UniversitÄts-Hautklinik, Inselspital, CH-3010, Bern, Switzerland

    A. Limat, T. Hunziker & L. R. Braathen

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  1. A. Limat
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  2. T. Hunziker
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  3. L. R. Braathen
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Limat, A., Hunziker, T. & Braathen, L.R. Effects of 1α,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs. Arch Dermatol Res 285, 402–409 (1993). https://doi.org/10.1007/BF00372133

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  • DOI: https://doi.org/10.1007/BF00372133

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