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  3. Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy

Tobacco toxins trigger bone marrow mesenchymal stem cells aging by inhibiting mitophagy

  • Ecotoxicol Environ Saf. 2024 Jun 1:277:116392. doi: 10.1016/j.ecoenv.2024.116392.
Kai Xiang 1,  Mingxing Ren 2,  Fengyi Liu 3,  Yuzhou Li 4,  Ping He 5,  Xuerui Gong 6,  Tao Chen 7,  Tianli Wu 8,  Ziyu Huang 9,  Hui She 10,  Kehao Liu 11,  Zheng Jing 12,  Sheng Yang 13
Affiliations

Affiliations

  • 1 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2021120672@stu.cqmu.edu.cn.
  • 2 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: renmingxing@stu.cqmu.edu.cn.
  • 3 Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address: 501521@hospital.cqmu.edu.cn.
  • 4 Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address: 501182@cqmu.edu.cn.
  • 5 Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address: kqhping@hospital.cqmu.edu.cn.
  • 6 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2021120630@stu.cqmu.edu.cn.
  • 7 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2021320046@stu.cqmu.edu.cn.
  • 8 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2022140188@stu.cqmu.edu.cn.
  • 9 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2022120660@stu.cqmu.edu.cn.
  • 10 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: eduemail@stu.cqmu.edu.cn.
  • 11 Stomatological Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 2023130346@stu.cqmu.edu.cn.
  • 12 Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address: 501042@hospital.cqmu.edu.cn.
  • 13 Stomatological Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Electronic address: 500283@cqmu.edu.cn.
PMID: 38677065 DOI: 10.1016/j.ecoenv.2024.116392
Abstract

Smoking disrupts bone homeostasis and serves as an independent risk factor for the development and progression of osteoporosis. Tobacco toxins inhibit the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), promote BMSCs aging and exhaustion, but the specific mechanisms are not yet fully understood. Herein, we successfully established a smoking-related osteoporosis (SROP) model in rats and mice through intraperitoneal injection of cigarette smoke extract (CSE), which significantly reduced bone density and induced aging and inhibited osteogenic differentiation of BMSCs both in vivo and in vitro. Bioinformatics analysis and in vitro experiments confirmed that CSE disrupts mitochondrial homeostasis through oxidative stress and inhibition of Mitophagy. Furthermore, we discovered that CSE induced BMSCs aging by upregulating phosphorylated Akt, which in turn inhibited the expression of FOXO3a and the Pink1/Parkin pathway, leading to the suppression of Mitophagy and the accumulation of damaged mitochondria. MitoQ, a mitochondrial-targeted antioxidant and Mitophagy agonist, was effective in reducing CSE-induced mitochondrial oxidative stress, promoting Mitophagy, significantly downregulating the expression of aging markers in BMSCs, restoring osteogenic differentiation, and alleviating bone loss and Autophagy levels in CSE-exposed mice. In summary, our results suggest that BMSCs aging caused by the inhibition of Mitophagy through the Akt/FOXO3a/Pink1/Parkin axis is a key mechanism in smoking-related osteoporosis.

Keywords

Aging; Bone marrow mesenchymal stem cells; Cigarette smoke extract; Mitophagy; Osteoporosis.

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