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Impact of Nicotine and PPARd-agonist on Human Mesenchymal Stem Cells

Bhat, Samerna
http://rave.ohiolink.edu/etdc/view?acc_num=mco1366337315

Abstract Details

2013, Master of Science in Biomedical Sciences (MSBS), University of Toledo, College of Medicine.
Smoking is a well established factor in many diseases and has multiple systemic effects due to more than 4000 different molecular species present in cigarette smoke. Osteoporosis, low bone mineral density, increased nonunion and delayed union, and increased risk of bone fracture have been associated with cigarette smoking. Nicotine, the main component of cigarette smoke is responsible for addiction. Previous studies have demonstrated deleterious impact of nicotine on skeletal remodeling and bone metabolism. Although many studies in the past have used osteoblasts and osteoblast like cells to study the impact of nicotine on bone, the use of human mesenchymal stem cells to determine the effects of nicotine has been rare. Therefore, learning whether or not these cells that go on to differentiate into osteoblasts and chondrocytes are also affected by nicotine will be particularly valuable in predicting the prognosis of a smoker undergoing orthopedic surgery/procedure. In this context, we examined the impact of nicotine in physiological range (0.1µM to 10 µM) on: a) hMSC proliferation b) Calcium deposition by osteoblasts (Alizarin red staining) c) Alkaline phosphatase activity (ALP assay on day) d) expression of canonical genes during differentiation of hMSCs (western blot analysis). Our results demonstrated a dose dependent decrease in hMSC proliferation, calcium deposition, ALP activity and expression of BMP-2 and HO-1. Interestingly, induction of heme oxygenase-1 (HO-1) by peroxisome proliferator-activated receptor delta (PPARd) agonist, GW0742, prevented the negative effect of nicotine. These results led to the conclusion that nicotine has a damaging effect on hMSCs proliferation and osteogenic differentiation and the induction of HO-1 by GW0742 results in the reversal of these effects. This offers an opportunity for HO-1 inducers to be used as therapeutic agents to improve bone fusion and fracture healing in smokers and non-smokers.
Nabil Ebraheim, MD (Committee Chair)
Jiayong Liu, MD (Committee Member)
Nitin Puri, MD, PhD (Committee Member)
75 p.
Biomechanics; Biomedical Research; Cellular Biology
mesenchymal stem cell; smoking; nicotine; PPARd-agonist; HO-1; BMP-2; ALP; osteoblast; Alizarin red staining

Recommended Citations

Citations

  • Bhat, S. (2013). Impact of Nicotine and PPARd-agonist on Human Mesenchymal Stem Cells [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1366337315

    APA Style (7th edition)

  • Bhat, Samerna. Impact of Nicotine and PPARd-agonist on Human Mesenchymal Stem Cells. 2013. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1366337315.

    MLA Style (8th edition)

  • Bhat, Samerna. "Impact of Nicotine and PPARd-agonist on Human Mesenchymal Stem Cells." Master's thesis, University of Toledo, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=mco1366337315

    Chicago Manual of Style (17th edition)

mco1366337315
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© 2013, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.
Release 3.2.12