Wang Guang, Li Hongming, Hu Xinyue, Wang Yiyi, Zhu Guoqiang, Zhou Hongliang, Liang Zilin, Wang Zhenxing, Nuessler Andreas, Lin Zhangyuan, Xie Hui, Zhu Sheng
Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China.
Movement System Injury and Repair Research Center, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China.
Heliyon. 2024 Aug 5;10(15):e35715. doi: 10.1016/j.heliyon.2024.e35715. eCollection 2024 Aug 15.
Smoking is by far one of the greatest public health threats and is recognized as an important predisposing factor for osteoporosis. Exposure to cigarette smoke (CS) has been reported to be associated with inflammation-associated diseases through the induction of pyroptosis. Nevertheless, the correlation between pyroptosis and bone loss induced by CS remains uninvestigated. Here, a mouse model of mainstream smoke exposure-induced osteoporosis was established. μCT, biomechanical testing, and immunohistochemical staining of bone tissue were used to assess the deleterious effects of CS on bone metabolism. , the effects of cigarette smoke extracts (CSE) on mouse primary bone marrow-derived mesenchymal stem cells (BMSCs) were tested by cell viability assays, gene and protein expression assays, and alizarin red staining. The utilization of the pyroptosis inhibitor MCC950 served to confirm the critical role of BMSCs pyroptosis in CS-induced osteoporosis. Our results indicated that exposure to mainstream smoke led to a notable decrease in the quantity of osteoblasts and hindered the process of osteogenic differentiation in mice. Additionally, there was a significant increase in the expression of pyroptosis-related proteins in the bone marrow. The inhibitory effects of CSE on cell viability and osteogenic differentiation of BMSCs were found to be dose-dependent . However, the presence of the pyroptosis inhibitor MCC950 significantly improved the impaired osteogenic differentiation and bone mineralization caused by CSE. These results highlight the crucial involvement of BMSCs pyroptosis in the development of bone loss induced by CS. In summary, the findings of this study provide novel evidence that CS exerts a detrimental effect on the process of osteogenesis in BMSCs through the induction of pyroptosis, ultimately leading to bone loss. Inhibition of pyroptosis effectively attenuated the toxicological effects of CS on BMSCs, providing a new target for preventing inflammatory osteoporosis.
吸烟是迄今为止最大的公共卫生威胁之一，被认为是骨质疏松症的一个重要诱发因素。据报道，接触香烟烟雾（CS）可通过诱导细胞焦亡与炎症相关疾病有关。然而，细胞焦亡与CS诱导的骨质流失之间的相关性仍未得到研究。在此，建立了一个主流烟雾暴露诱导的骨质疏松症小鼠模型。采用μCT、生物力学测试和骨组织免疫组化染色来评估CS对骨代谢的有害影响。此外，通过细胞活力测定、基因和蛋白质表达测定以及茜素红染色来测试香烟烟雾提取物（CSE）对小鼠原代骨髓间充质干细胞（BMSC）的影响。使用细胞焦亡抑制剂MCC950来证实BMSC焦亡在CS诱导的骨质疏松症中的关键作用。我们的结果表明，接触主流烟雾导致小鼠成骨细胞数量显著减少，并阻碍了成骨分化过程。此外，骨髓中细胞焦亡相关蛋白的表达显著增加。发现CSE对BMSC的细胞活力和成骨分化的抑制作用具有剂量依赖性。然而，细胞焦亡抑制剂MCC950的存在显著改善了CSE引起的受损成骨分化和骨矿化。这些结果突出了BMSC焦亡在CS诱导的骨质流失发展中的关键作用。总之，本研究结果提供了新的证据，表明CS通过诱导细胞焦亡对BMSC的成骨过程产生有害影响，最终导致骨质流失。抑制细胞焦亡有效地减轻了CS对BMSC的毒理学作用，为预防炎症性骨质疏松症提供了新的靶点。
