Journal of Bone and Mineral Metabolism

, Volume 31, Issue 1, pp 44–52 | Cite as

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

  • Dong Hyun Kim
  • Jiayong Liu
  • Samerna Bhat
  • Gregory Benedict
  • Beata Lecka-Czernik
  • Stephen J. Peterson
  • Nabil A. Ebraheim
  • Bruce E. Heck
Original article


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.


PPARδ HO-1 Nicotine Osteogenesis 


Conflict of interest

This work was supported by National Institutes of Health grants DK068134, HL55601, and HL-34300 from Dr. Nader G. Abraham. All authors have read and agree with the manuscript as written and have no any conflict of interest.


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2012

Authors and Affiliations

  • Dong Hyun Kim
    • 1
  • Jiayong Liu
    • 2
  • Samerna Bhat
    • 2
  • Gregory Benedict
    • 2
  • Beata Lecka-Czernik
    • 1
    • 2
  • Stephen J. Peterson
    • 3
  • Nabil A. Ebraheim
    • 2
  • Bruce E. Heck
    • 1
  1. 1.Department of Physiology and PharmacologyUniversity of Toledo College of MedicineToledoUSA
  2. 2.Department of OrthopaedicsUniversity of Toledo Medical CenterToledoUSA
  3. 3.Department of MedicineNew York Medical CollegeNew YorkUSA

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