In vitro evaluation of the direct effect of estradiol on human osteoblasts (HOB) and human mesenchymal stem cells (h-MSCs) Lucy DiSilvio a , Jacqueline Jameson a , Zakareya Gamie b , Peter V. Giannoudis b , Eleftherios Tsiridis a,b, * a Department of Biomaterial and Biomimetics, Guy’s, King’s and St Thomas’ Dental Institute, University of London, London SE1 1UL, UK b Academic Department of Trauma & Orthopaedics St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK Introduction The current high prevalence of morbidity associated with osteoporosis has made it an important public- health and economic issue. 15,27,31 Estrogen defi- ciency is critical to the pathogenesis of osteoporo- sis 30 and its effect is thought to be largely limited to the first 5 years after the menopause. 1 Osteoporosis is characterised by an accelerated remodelling process with markers of both bone formation and resorption increasing. Estrogen treatment decreases the rate of bone remodelling and the Injury, Int. J. Care Injured (2006) 37S, S33—S42 www.elsevier.com/locate/injury KEYWORDS Estrogen; Osteoblasts; Proliferation; Bone; Receptor; Formation Summary Estrogen may increase the proliferation of osteoblasts depending upon their differentiation stage. Our objective was to test the hypothesis that estradiol could stimulate the proliferation of primary human osteoblast (HOB) cells or human mesenchymal stem cells (h-MSCs). To test this hypothesis, we investigated two synthetic estradiol preparations: (a) a commercially available one (in clinical use) whose effect was evaluated using MTTassay, trypan blue cell counts and total protein assays; (b) a novel synthetic preparation (not in clinical use) using Alamar Blue assays and scanning electron microscopy (SEM). Commercial estradiol increased HOB pro- liferation in a concentration-dependant manner between 1 nM and 8 nM reaching significance at a concentration of 8 nM ( p < 0.001). Small doses of 1 nM and 2 nM increased h-MSC proliferation ( p < 0.001) but higher doses had no effect. All novel synthetic estradiol preparations decreased HOB proliferation ( p < 0.001) whereas no direct effect was observed on h-MSCs. Commercial estradiol appears to induce proliferation of HOBs, although its effects on h-MSCs appears to be highly dose- dependent and requires further investigation. # 2006 Elsevier Ltd. All rights reserved. * Corresponding author. Tel.: +44 113 20 66460; fax: +44 113 20 65156. E-mail address: etsiridis@doctors.org.uk (E. Tsiridis). 0020–1383/$ — see front matter # 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2006.08.022