Exploring the relationship between pyroptosis and inflammatory bone loss: Evidence from a cigarette smoke-induced osteoporosis mouse model
Guang Wang,
Hongming Li,
Xinyue Hu,
Yiyi Wang,
Guoqiang Zhu,
Hongliang Zhou,
Zilin Liang,
Zhenxing Wang,
Andreas Nuessler,
Zhangyuan Lin,
Hui Xie,
Sheng Zhu
Affiliations
Guang Wang
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
Hongming Li
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
Xinyue Hu
Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Yiyi Wang
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
Guoqiang Zhu
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
Hongliang Zhou
Movement System Injury and Repair Research Center, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Zilin Liang
Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Zhenxing Wang
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; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Andreas Nuessler
Department of Trauma and Reconstructive Surgery, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076, Tuebingen, Germany
Zhangyuan Lin
Department of Orthopedics, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Hui Xie
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; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
Sheng Zhu
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; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China; Corresponding author. Department of Orthopedics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, Hunan, China.
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. In vitro, 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 in vitro. 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.
