Nicotine and Cotinine Inhibit Catalase and Glutathione Reductase Activity Contributing to the Impaired Osteogenesis of SCP-1 Cells Exposed to Cigarette Smoke
Open accessAbstract
Cigarette smoking has been identified as a major risk factor for osteoporosis decades ago. Several studies have shown a direct relationship between cigarette smoking, decreased bone mineral density, and impaired fracture healing. However, the mechanisms behind impaired fracture healing and cigarette smoking are yet to be elucidated. Migration and osteogenesis of mesenchymal stem/stromal cells (MSCs) into the fracture site play a vital role in the process of fracture healing. In human nicotine, the most pharmacologically active and major addictive component present in tobacco gets rapidly metabolized to the more stable cotinine. This study demonstrates that physiological concentrations of both nicotine and cotinine do not affect the osteogenic differentiation of MSCs. However, cigarette smoke exposure induces oxidative stress by increasing superoxide radicals and reducing intracellular glutathione in MSCs, negatively affecting osteogenic differentiation. Although, not actively producing reactive oxygen species (ROS) nicotine and cotinine inhibit catalase and glutathione reductase activity, contributing to an accumulation of ROS by cigarette smoke exposure. Coincubation with N‐acetylcysteine or L‐ascorbate improves impaired osteogenesis caused by cigarette smoke exposure by both activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling and scavenging of ROS, which thus might represent therapeutic targets to support fracture healing in smokers.
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Osteogenic differentiation of mesenchymal stem cells is not largely altered when exposed to nicotine at concentrations similar to its serum levels in smokers.
“Aspera-Werz et al. showed that the osteogenic differentiation of MSCs was not largely altered when the cells were exposed to nicotine at concentrations similar to its serum levels in smokers [64].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [64]
Nrf2 directly modulates antioxidant defense systems in human mesenchymal stem cells exposed to cigarette smoke extract.
“Aspera-Werz et al.reported that Nrf2 directly modulates antioxidant defense systems in human mesenchymal stem cells exposed to CSE [64]”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [64]
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- Authors
- Aspera-Werz, R. H., Ehnert, S., Heid, D., Zhu, S., Chen, T., Braun, B., Sreekumar, V., Arnscheidt, C., & Nussler, A. K.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Nussler, Andreas K.
- ORCID
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2018-01
- Volume
- 2018
- Issue
- 1
- Pages
- 3172480-3172480
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC6250005
- OpenAlex
- W2899604438
- Cited by
- 90
- References
- 65
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 21 · 2021: 15 · 2020: 8 · 2019: 7 · 2017: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Elsbeth Bonhoff Foundation (D.30.21114)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- nicotine, cotinine, cigarette smoke, osteogenic differentiation, mesenchymal stem cells, catalase, glutathione reductase, oxidative stress, reactive oxygen species, Nrf2 signaling, N-acetylcysteine, L-ascorbate, fracture healing, osteoporosis, smokers
- MeSH terms
- Antioxidants, Catalase, Cell Differentiation, Cell Line, Cotinine, Glutathione Reductase, Humans, Nicotine, Osteogenesis, Smoke, Reactive Oxygen Species, Mesenchymal Stem Cells, Tobacco Products
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