摘要
细胞焦亡(Pyroptosis)是伴炎症反应的程序性死亡方式,Gasdermin D(GSDMD)是介导细胞焦亡的关键蛋白,也是主要执行者。当病原微生物等刺激炎性小体后,激活焦亡信号半胱天冬氨酸蛋白酶(caspase),使其切割GSDMD,然后GSDMD的氨基末端(N端)转移至细胞膜上形成允许水分子等物质进入的细胞内孔隙,从而引起细胞肿胀及裂解,导致细胞死亡,即细胞焦亡。近年来科学研究进展发现,GSDMD可能通过介导成骨细胞焦亡参与了骨代谢疾病特别是骨质疏松症的发病机制,抑制成骨细胞焦亡可调控骨质疏松症的发展。成骨细胞焦亡或许作为一种促炎性调控骨细胞死亡的方式干预骨代谢,而且对其研究是当下新颖的科研热点。笔者从细胞焦亡分析并探讨GSDMD介导成骨细胞焦亡的分子机制,对其与细胞焦亡领域之间的关系进行综述,分析成骨细胞焦亡与骨质疏松疾病之间的联系,为骨质疏松症的研究和诊疗提供关键的靶点蛋白因子机制。
Pyroptosis is a programmed cell death with inflammatory response.Gasdermin D(GSDMD)is a key protein that mediates pyroptosis and is the main executor.When inflammasomes are stimulated by pathogenic microorganisms,the pyroptosis signal caspase is activated,which cuts GSDMD.Then the amino terminal(N terminal)of GSDMD is transferred to the cell membrane to form intracellular pores that allow water molecules and other substances to enter,causing cell swelling and cracking,leading to cell death,that is,cell pyroptosis.In recent years,scientific research has demonstrated that GSDMD may be involved in the pathogenesis of bone metabolic diseases,especially osteoporosis,by mediating osteoblast pyroptosis.Inhibition of osteoblast pyroptosis may regulate the development of osteoporosis.Osteoblast pyroptosis may interfere with bone metabolism as a pro-inflammatory way to regulate osteocyte death,and its research is a new research hot spot.In this paper,the molecular mechanism of GSDMD-mediated osteoblast pyroptosis is analyzed and discussed,and the relationship between GSDMD-mediated osteoblast pyroptosis and the field of cell pyroptosis is reviewed.The relationship between osteoblast pyroptosis and osteoporosis is analyzed,which provides a key target protein factor mechanism for the research and diagnosis and treatment of osteoporosis.
作者
麻永胜
王立强
蒋宜伟
周玉英
马晨光
宋重东
刘沛
马俊飞
史达
MA Yongsheng;WANG Liqiang;JIANG Yiwei;ZHOU Yuying;MA Chenguang;SONG Chongdong;LIU Pei;MA Junfei;SHI Da(Gansu University of Traditional Chinese Medicine,Lanzhou 730000;Key Laboratory of Dunhuang Medicine,Ministry of Education,Lanzhou 730000;The Affiliated Hospital of Gansu University of Traditional Chinese Medicine,Lanzhou 730000;Xi′an Honghui Hospital,Xi′an 710054,China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2024年第7期1028-1032,1055,共6页
Chinese Journal of Osteoporosis
基金
国家自然科学基金(82160916)
敦煌医学与转化教育部重点实验室开放课题(DHYX22-03)
甘肃省自然科学基金(23JRRA1713)
甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金项目(2021)
兰州市科技计划项目(2023-ZD-215)
甘肃省高等学校创新能力提升项目(2019B-107)
甘肃省中医药管理局科研课题(GZK-2017-17)。
