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01-01-2013 | Original article

Peroxisome proliferator-activated receptor delta agonist attenuates nicotine suppression effect on human mesenchymal stem cell-derived osteogenesis and involves increased expression of heme oxygenase-1

Authors: Dong Hyun Kim, Jiayong Liu, Samerna Bhat, Gregory Benedict, Beata Lecka-Czernik, Stephen J. Peterson, Nabil A. Ebraheim, Bruce E. Heck

Published in: Journal of Bone and Mineral Metabolism | Issue 1/2013

Abstract

Smoking has long been associated with osteoporosis, decreased bone mineral density, increased risk of bone fracture, and increased health costs. Nicotine, the main component of cigarette smoke, has major negative effects on bone metabolism and skeletal remodeling in vivo. Although osteoblasts and osteoblast-like cells have been used extensively to study the impact of nicotine, few studies have been performed on human mesenchymal stem cells (hMSCs). In this context, we examined the impact of nicotine on (a) hMSCs proliferation, (b) osteoblastic differentiation, (c) alkaline phosphatase (ALP) activity, and (d) expression of canonical genes during differentiation of hMSCs. MSCs isolated from human bone marrow were treated with different concentrations (0, 0.1, 1 and 10 μM) of nicotine for 7 days. Nicotine caused a dose-dependent decrease in cell proliferation, decreased heme oxygenase-1 (HO-1) expression (p < 0.05) and attenuated osteogenesis (p < 0.05) in hMSCs (45 % reduction at day 14). In addition, nicotine caused a dose-dependent decrease in alizarin red staining for calcium and staining for ALP. Induction of HO-1 by peroxisome proliferator-activated receptor delta agonist (GW0742) prevented the effect of nicotine. Nicotine caused a dose-dependent reduction in the expression of BMP-2, a well-known marker for bone formation; however, this was prevented by GW0742 treatment. Therefore, induction of HO-1 prevents the deleterious effects of nicotine on osteogenesis in hMSC. This offers insight into both how nicotine affects bone remodeling and a therapeutic approach to prevent fracture and osteoporosis in smokers.

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Title: Peroxisome proliferator-activated receptor delta agonist attenuates nicotine suppression effect on human mesenchymal stem cell-derived osteogenesis and involves increased expression of heme oxygenase-1
Authors: Dong Hyun Kim
Jiayong Liu
Samerna Bhat
Gregory Benedict
Beata Lecka-Czernik
Stephen J. Peterson
Nabil A. Ebraheim
Bruce E. Heck
Publication date: 01-01-2013
Publisher: Springer Japan
Published in: Journal of Bone and Mineral Metabolism / Issue 1/2013
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-012-0382-0

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