摘要
背景:研究表明,骨细胞的程序性死亡与激素性股骨头缺血坏死之间具有一定的相关性,且细胞自噬及凋亡之间存在相互作用,内质网应激通路参与调控骨细胞自噬及凋亡过程。目的:综述内质网应激调控细胞自噬与凋亡的相关通路,总结细胞自噬与凋亡通路在激素性股骨头缺血坏死发病机制中的研究进展。方法:由第一作者使用计算机检索PubMed数据库、Web of Science数据库、CNKI数据库、万方数据库中从建库至2020年5月的相关文献,检索词分别为“steroid;necrosis of the femoral head;cell autophagy;ER stress;unfolded protein response”和“糖皮质激素;股骨头坏死;细胞自噬;细胞凋亡;内质网应激;未折叠蛋白反应”。选择与细胞自噬、细胞凋亡调控激素性股骨头坏死与内质网应激通路有关的文章,排除重复与较陈旧的文献以及Meta分析。结果与结论:内质网应激主要通过PERK/eIF2α途径、IRE1-TRAF2-JNK途径以及调控细胞内Ca^(2+)浓度对细胞自噬起调控作用。内质网应激通过激活PERK/eIF2α途径中C/EBP同源蛋白(CHOP)、IRE1α-ASK1-JNK通路、IRE1α-XBP1-CHOP通路、激活Caspase-12通路调控细胞凋亡。轻度内质网应激时,内质网可通过激活未折叠蛋白反应途径启动自噬以恢复内质网稳态,促使细胞存活;当内质网应激刺激过强且持续存在时,会过度诱导自噬或激活凋亡途径使细胞死亡。内质网应激可通过多种信号通路参与细胞自噬即凋亡的调控;细胞自噬和细胞凋亡之间存在一个复杂的相互作用过程,在激素性股骨头缺血坏死发病机制中,内质网应激参与调控骨细胞及成骨细胞程序性死亡,但具体机制尚不明确。
BACKGROUND:Studies have shown that there is a certain correlation between programmed osteocyte death and steroid-induced avascular necrosis of the femoral head,and there is an interaction between autophagy and apoptosis.Endoplasmic reticulum stress pathway is involved in the regulation of osteocyte autophagy and apoptosis.OBJECTIVE:To review the related pathways of autophagy and apoptosis regulated by endoplasmic reticulum stress,and summarize the research progress of autophagy and apoptosis pathways in the pathogenesis of steroid-induced avascular necrosis of the femoral head.METHODS:A computer-based online retrieval of PubMed,Web of Science,CNKI and WanFang databases was performed for relevant literatures published from database inception to May 2020 with the keywords of“steroid;necrosis of the femoral head;cell autophagy;ER stress;unfolded protein response”in Chinese and English,respectively.The articles concerning autophagy and apoptosis regulating steroid-induced avascular necrosis of the femoral head related to endoplasmic reticulum stress pathways were included,and the redundant and old articles or Meta-analysis were excluded.RESULTS AND CONCLUSION:Endoplasmic reticulum stress regulates autophagy mainly through PERK/eIF2αpathway,IRE1-TRAF2-JNK pathway and regulation of intracellular Ca^(2+)concentration.Endoplasmic reticulum stress regulates apoptosis by activating C/EBP homologous protein of PERK/eIF2αpathway,IRE1α-ASK1-JNK pathway,IRE1α-XBP1-CHOP pathway and Caspase-12 pathway.In mild endoplasmic reticulum stress,the endoplasmic reticulum can initiate autophagy by activating unfolded protein response pathway to restore endoplasmic reticulum homeostasis and promote cell survival.Endoplasmic reticulum stress stimulation that is too strong and persistent will over-induce autophagy or activate apoptosis pathway to cause cell death.Endoplasmic reticulum stress can participate in the regulation of autophagy or apoptosis through a variety of signal pathways;there is a complex interaction between autophagy and apoptosis.Endoplasmic reticulum stress is involved in the regulation of programmed death of osteocytes and osteoblasts in the pathogenesis of steroidinduced avascular necrosis of the femoral head,but the specific mechanism is not clear.
作者
赵千增
赵振群
刘万林
Zhao Qianzeng;Zhao Zhenqun;Liu Wanlin(Graduate School of Inner Mongolia Medical University,Hohhot 010000,Inner Mongolia Autonomous Region,China;The Second Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010030,Inner Mongolia Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第29期4685-4690,共6页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(81960397),项目负责人:刘万林
国家自然科学基金项目(81760391),项目负责人:赵振群
内蒙古自治区高等学校“青年科技英才支持计划”项目(NJYT-20-B04),项目负责人:赵振群。
关键词
激素性股骨头缺血坏死
内质网应激
未折叠蛋白反应
细胞自噬
细胞凋亡
骨细胞
信号通路
综述
steroid-induced avascular necrosis of the femoral head
endoplasmic reticulum stress
unfolded protein response
autophagy
apoptosis
osteocyte
signaling pathway
review
