摘要
骨质疏松症作为慢性代谢性骨骼疾病,主要由成骨与破骨细胞之间的失衡造成骨稳态紊乱。线粒体自噬是一种重要的细胞清除方式,能够有效地清除损伤或无用的线粒体,从而维持细胞的稳态。生理情况下,骨骼中线粒体自噬可以满足各骨细胞的功能性需求,同时对自身进行清除或更新,维持骨细胞稳态。相反,失调的线粒体自噬可能触发骨骼细胞死亡,尤其是焦亡的发生,失调的线粒体自噬可以激活NLRP3炎症小体继而促进骨骼细胞的焦亡,释放炎症因子,加重内环境的紊乱,促进骨质疏松的发生发展。因此,阐明线粒体自噬与细胞焦亡的内在机制联系,有助于进一步研究靶向线粒体自噬介导的骨骼细胞焦亡以治疗骨质疏松的药物。本文概述了在正常的骨重塑活动和骨质疏松中线粒体自噬参与调节细胞焦亡的最新机制,以期为未来的基础研究及临床应用提供思考。
Osteoporosis is a chronic metabolic bone disease that is mainly caused by the imbalance between osteoblasts and osteoclasts.Mitophagy is an important form of cellular clearance,which effectively removes damaged or useless mitochondria to maintain cellular homeostasis.Under physiological conditions,mitochondrial autophagy in bones can meet the functional needs of each bone cell,and at the same time clear or renew itself to maintain bone cell homeostasis.On the contrary,dysregulated mitophagy may trigger the death of skeletal cells,especially pyroptosis,and dysregulated mitophagy can activate NLRP3 inflammasomes and then promote pyroptosis of skeletal cells,release inflammatory factors,aggravate the disorder of the internal environment,and promote the occurrence and development of osteoporosis.Therefore,elucidating the intrinsic mechanistic link between mitophagy and pyroptosis is helpful for further research on drugs targeting mitophagy-mediated pyroptosis in skeletal cells for the treatment of osteoporosis.This article summarizes the latest mechanism of mitophagy involved in the regulation of pyroptosis in normal bone remodeling activities and osteoporosis,in order to provide thoughts for future basic research and clinical applications.
作者
任凯
娄纯彪
李宗玉
马国栋
李志超
曹慧
臧铭鉴
REN Kai;LOU Chunbiao;LI Zongyu;MA Guodong;LI Zhichao;CAO Hui;ZANG Mingjian(Haiyang People’s Hospital,Yantai 265100,China;Shandong University of Traditional Chinese Medicine,Ji′nan 250014,China;The 960th Hospital,Joint Logistics Support Force of PLA,Ji′nan 250014,China)
出处
《中国骨质疏松杂志》
北大核心
2025年第12期1818-1823,共6页
Chinese Journal of Osteoporosis
基金
国家自然科学基金面上项目(82374620)。
关键词
骨质疏松
线粒体自噬
细胞焦亡
osteoporosis
mitochondrial autophagy
pyroptosis
