Evaluation of beneficial and adverse effects of glucocorticoids on a newly developed full-thickness skin model

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

“…In clinical practice, glucocorticoids are probably the most well known drugs that cause marked side-effects via their influence on the ECM. Systemic use of glucocorticoids for a longer period of time in the treatments of chronic inflammatory disease processes is almost inevitably harmful to healthy tissues (McDonough et al, 2008), particularly bones, by causing premature or ex-TARGETING EXTRACELLULAR MATRIX MOLECULES IN PHARMACOTHERAPY 209 aggerated osteoporosis (Ton et al, 2005;Canalis et al, 2007), and skin, by inducing its thinning (Schoepe et al, 2006;Zöller et al, 2008). Recent developments in bone biology have markedly advanced our understanding of how glucocorticoids affect the receptor activator of the nuclear factor-B-ligand-osteoprotegerin system and the Wnt-catenin signaling pathway (Berris et al, 2007;Canalis et al, 2007) and via these effects favor osteoclastogenesis instead of osteoblastogenesis.…”

Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

“…Consequently, they allow medium or even high throughput compound screening and are, thus, highly attractive in FTSM: epidermal thinning, reduced proliferation of keratinocytes in stratum basale, inhibition of collagen type I and III and MMP-1 and -3 synthesis. 22,23 In addition to their undesired effects, the beneficial effects of GCs may be determined within the same experimental model by measurement of stimulusinduced interleukin-6 and -8 secretion into medium. 23 The benefit of skin tissue models compared to monolayer cell systems or animal experiments are (1) the human origin of the cells, (2) the warranted interactions of keratinocytes and fibroblasts and (3) the reduced variability of read out parameters ( Table 1).…”

“…21 Recently, epidermal thickness and collagen synthesis in three-dimensional full-thickness skin models (FTSM) were developed to determine GC ligand induced skin atrophy in vitro. 22,23 In vivo, the hairless OFA hr/ hr rat, however, is still the gold standard model for GC-induced skin atrophy in basic and pharmaceutical research. 18,24 The purpose of this review is to summarize the current atrophy models and to highlight further perspectives.…”

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

“…Glucocorticoid induced anti-inflammatory effects (decline of interleukin-6 and interleukin-8 secretion, histological analysis) were seen following the induction of inflammation by UVB irradiation or TNFα exposure. Unwanted effects were observable by a decline in collagen amounts (Weindl et al, 2011;Zöller et al, 2008), which reflects the most relevant adverse effect of long-term topical glucocorticoid therapy, i.e., skin atrophy.…”