ArticleInternational journal of molecular sciences2019
Cigarette Smoke Induces the Risk of Metabolic Bone Diseases: Transforming Growth Factor Beta Signaling Impairment via Dysfunctional Primary Cilia Affects Migration, Proliferation, and Differentiation of Human Mesenchymal Stem Cells.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research.International journal of molecular sciences · 2019Pooled it
- Mesenchymal stromal cells in human immunodeficiency virus-infected patients with discordant immune response: Early results of a phase I/II clinical trial.Stem cells translational medicine · 2021Trial
- Fracture healing: from molecular and cellular mechanisms to therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation.Stem cell reports · 2026Article
- Human Primary Mesenchymal Stem Cells Fail to Recover Full Osteogenic Differentiation Potential Following Washout of Electronic Cigarette Aerosol Extracts.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2026Article
- Article
- Preliminary study on the potential damage of cigarette smoke extract in 3D human chondrocyte culture.In vitro cellular & developmental biology. Animal · 2025Article
- Acute exposure to electronic cigarette components alters mRNA expression of pre-osteoblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis.Journal of orthopaedic translation · 2024Review
- Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy.Stem cell research & therapy · 2024Article
- Herbal Extracts of Ginseng and Maqui Berry Show Only Minimal Effects on an In Vitro Model of Early Fracture Repair of Smokers.Foods (Basel, Switzerland) · 2023Article
- Maqui Berry and Ginseng Extracts Reduce Cigarette Smoke-Induced Cell Injury in a 3D Bone Co-Culture Model.Antioxidants (Basel, Switzerland) · 2022Article
- Searching for the Optimal Donor for Allogenic Adipose-Derived Stem Cells: A Comprehensive Review.Pharmaceutics · 2022Review
- Microcurrent Reverses Cigarette Smoke-Induced Angiogenesis Impairment in Human Keratinocytes In Vitro.Bioengineering (Basel, Switzerland) · 2022Article
- In vitro modeling of liver fibrosis in 3D microtissues using scalable micropatterning system.Archives of toxicology · 2022Article
- Article
- Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome.Frontiers in immunology · 2022Review
- Cigarette Smoke Exposure Inhibits Osteoclast Apoptosis via the mtROS Pathway.Journal of dental research · 2021Article
- Primary cilia in hard tissue development and diseases.Frontiers of medicine · 2021Review
- Stem cells' centrosomes: How can organelles identified 130 years ago contribute to the future of regenerative medicine?World journal of stem cells · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well established that smoking has detrimental effects on bone integrity and is a preventable risk factor for metabolic bone disorders. Following orthopedic surgeries, smokers frequently show delayed fracture healing associated with many complications, which results in prolonged hospital stays. One crucial factor responsible for fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSCs) at early stages, a mechanism mediated by transforming growth factor β (TGF-β). Although it is known that smokers frequently have decreased TGF-β levels, little is known about the actual signaling occurring in these patients. We investigated the effect of cigarette smoke on TGF-β signaling in MSCs to evaluate which step in the pathway is affected by cigarette smoke extract (CSE). Single-cell-derived human mesenchymal stem cell line (SCP-1 cells) were treated with CSE concentrations associated with smoking up to 20 cigarettes a day. TGF-β signaling was analyzed using an adenovirus-based reporter assay system. Primary cilia structure and downstream TGF-β signaling modulators (Smad2, Smad3, and Smad4) were analyzed by Western blot and immunofluorescence staining. CSE exposure significantly reduced TGF-β signaling. Intriguingly, we observed that protein levels of phospho-Smad2/3 (active forms) as well as nuclear translocation of the phospho-Smad3/4 complex decreased after CSE exposure, phenomena that affected signal propagation. CSE exposure reduced the activation of TGF-β modulators under constitutive activation of TGF-β receptor type I (ALK5), evidencing that CSE affects signaling downstream of the ALK5 receptor but not the binding of the cytokine to the receptor itself. CSE-mediated TGF-β signaling impaired MSC migration, proliferation, and differentiation and ultimately affected endochondral ossification. Thus, we conclude that CSE-mediated disruption of TGF-β signaling in MSCs is partially responsible for delayed fracture healing in smokers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.