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Low doses amino-bisphosphonates stimulate keratinocytes growth inactivating glucocorticoid receptor

Low doses amino-bisphosphonates stimulate keratinocytes growth inactivating glucocorticoid receptor

Journal Reference

Renò F, Rizzi M, Invernizzi M, Migliario M, Cisari C.

Eur J Pharmacol. 2013 Dec 5;721(1-3):301-4.

Innovative Research Laboratory for Wound Healing, Health Sciences Department, University of Eastern Piedmont “A. Avogadro”, via Solaroli 17, 28100 Novara, Italy. Electronic address: [email protected]

Abstract

 

Amino-bisphosphonates (N-BPs) are widely employed to treat a great variety of clinical conditions characterized by altered calcium metabolism, such as bone diseases. Their mechanism of action relies on the lowering of farnesyl pyrophosphate (FPP) endogenous levels by inhibiting FPP synthase. It is known that in epithelial cells FPP reduces both cell proliferation and migration by activating glucocorticoid receptor. In this study human keratinocytes (HaCaT cells) were treated with low concentrations (100 nM – 10 uM) of two Amino-bisphosphonates (zoledronate (Zol) and neridronate (Ner)) to investigate drugs effects on cellular proliferation and glucocorticoid receptor activation. When used at low concentrations, close to their IC50 for FPP synthase, both Zol and Ner were able to stimulate human keratinocytes proliferation through a reduction of glucocorticoid receptor activation. The proposed mechanism accounts for the ability of low concentrations of zoledronate and neridronate to stimulate human keratinocytes proliferation, fostering new clinical applications for these “old” drugs in the field of epithelial regeneration.

 

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