Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (11): 1759-1765.doi: 10.3969/j.issn.2095-4344.3104
Previous Articles Next Articles
Zhang Xujian1, Zhao Zhenqun2, Liu Wanlin2
Received:
2020-07-16
Revised:
2020-07-24
Accepted:
2020-08-19
Online:
2021-04-18
Published:
2020-12-22
Contact:
Liu Wanlin, Master, Chief physician, MD/Master’s supervisor, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
Co-corresponding author: Zhao Zhenqun, MD, Chief physician, Master’s supervisor, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia Autonomous Region, China
About author:
Zhang Xujian, Master candidate, Graduate School of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
Supported by:
CLC Number:
Zhang Xujian, Zhao Zhenqun, Liu Wanlin. The role of endoplasmic reticulum stress in the pathogenesis of steroid-induced avascular necrosis of the femoral head [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1759-1765.
2.1 内质网生理学 内质网在脂质、蛋白质合成中起着核心作用,并通过控制Ca2+的运动来调控几条信号通路。内质网是由一系列连续的膜组成的,这些膜被组织成亚域,包括粗糙的、平滑的、过渡的内质网以及核膜。粗面内质网主要为片层状,与多聚核糖体有关,参与蛋白质合成和Ca2+信号传导。光滑的内质网主要由提供脂质生物合成场所的管状结构组成,在Ca2+信号传导中起主要作用,并被称为与其他细胞器的主要接触点[13]。 内质网是各种脂质(包括磷脂、胆固醇和神经酰胺)的主要细胞生物合成室,随后通过分泌途径的小泡转运到其他细胞器和细胞膜[14]。内质网参与监测脂质膜的组成,帮助激活适当的反应以维持脂质的动态平衡。新合成的蛋白质被转移到内质网进行特定的修饰,包括折叠、糖基化和二硫键的形成[15]。内质网质量控制系统通过促进不正确折叠多肽的正确折叠或选择性降解它们来防止错误的蛋白质聚集[16],各种内质网功能紧密地联系在一起,例如,错误折叠蛋白质的积累可以改变Ca2+的动态平衡,而Ca2+管腔含量的变化又对蛋白质合成过程有重大影响[17]。真核细胞中多达30%的蛋白质以分泌途径为目标,准备分泌的蛋白质被转位穿过或插入内质网膜,在被运输到高尔基体之前,它们折叠和组装到它们的自然状态;不能正确折叠的蛋白质会通过内质网膜转回到胞浆中,在那里它们作为底物被降解,这个过程称为内质网相关降解[18]。 内质网既可以接收信号,也可以发送信号。输入信号包括Ca2+,1,4,5-三磷酸肌醇、1-磷酸鞘氨醇、活性氧和固醇,为了响应这些输入信号,内质网生成各种输出信号,例如Ca2+瞬变、存储操作通道的激活剂、应激信号、花生四烯酸代谢产物和各种转录因子(核因子κB、增强子结合蛋白同源蛋白、激活转录因子6和固醇调节元件结合蛋白)。细胞器形态的结构差异与内质网功能的差异相关[13]。如上所述,内质网是蛋白质折叠和成熟的纽带,这些蛋白质通过分泌途径进行折叠和成熟。蛋白质折叠既受内质网常驻分子伴侣的调控,也受其感知,例如葡萄糖调节蛋白78和葡萄糖调节蛋白94[19]。葡萄糖调节蛋白78是一种相对分子质量78 000的蛋白质,在缺乏葡萄糖的培养基中生长的培养细胞中其合成得到增强。随后,葡萄糖调节蛋白78被确定为是一种内质网驻留蛋白,其合成可能受到各种环境和生理应激条件的刺激,从而干扰内质网功能和动态平衡。葡萄糖调节蛋白78,通常称为BiP,为一种免疫球蛋白重链结合蛋白,是公认的内质网应激标记物[20]。与葡萄糖调节蛋白78一样,葡萄糖调节蛋白94也参与蛋白质折叠,与内质网蛋白质折叠机制的其他组件相互作用,控制钙的储存,并协助将错误折叠的蛋白质降解[21];与葡萄糖调节蛋白78相比,葡萄糖调节蛋白94的靶向蛋白更具选择性,在免疫、生长信号和细胞黏附中起关键作用。 2.2 内质网应激中的未折叠蛋白反应及其信号通路 内质网是一个与核膜连续的膜性网络,是钙储存、脂质合成和蛋白质稳态(合成、折叠、修饰、运输和降解)的场所[22]。由于蛋白质折叠的复杂性,它是基因表达中最容易出错的一步[23]。因此,机体进行内质网相关降解和/或自噬,来降解错误折叠的蛋白质或激活未折叠蛋白反应,未折叠蛋白反应是一种适应性机制,可以在内质网中重新建立蛋白平衡。葡萄糖调节蛋白78通常与3种跨膜蛋白结合并使其失活,它们分别是蛋白激酶R样内质网激酶(protein kinase R(PKR)-like endoplasmic reticulum kinase,PERK)、肌醇需要酶1α(inositol requiring enzyme 1α,IRE1α)和激活转录因子6[24]。当内质网应激发生时,错误折叠的蛋白积聚,葡萄糖调节蛋白78就会从这些跨膜蛋白中分离出来,并结合错误折叠的蛋白来正确折叠它们,由此引发未折叠蛋白反应。未折叠蛋白反应包括3条信号通路:PERK信号通路、IRE1α信号通路和激活转录因子6信号通路[25],如图2所示。 在内质网“稳态”状态下,内质网维持蛋白质和Ca2+稳态;在内质网“应激”状态下,错误折叠蛋白的积累诱导PERK、IRE1α和激活转录因子6释放伴侣蛋白(BiP)。这些通路可随后在未折叠蛋白反应的信号级联中被激活,包括下调翻译蛋白和激活转录因子,这些转录因子调节靶基因以促进内质网稳态和细胞存活。 第一条通路是PERK信号通路。PERK信号通路是最先被激活,也是早期在内质网应激中起主要保护的通路[26]。内质网应激发生时,激活的PERK磷酸化其下游的真核翻译起始因子2α,磷酸化的真核翻译起始因子2α减少了蛋白质翻译,从而减少了内质网折叠蛋白质的负担[27]。PERK激活还导致激活转录因子4和CCAAT/增强子结合蛋白同源蛋白的优先翻译,这2个转录因子转位到细胞核增加葡萄糖调节蛋白78、生长停滞与DNA损伤可诱导蛋白34和凋亡基因的表达[28-29]。内质网应激的促凋亡作用主要通过激活PERK-真核翻译起始因子2-激活转录因子4-增强子结合蛋白同源蛋白-Bcl-2通路来实现[27],且与多种疾病的发生和发展有关[30-31],其中,增强子结合蛋白同源蛋白在内质网应激诱导的凋亡过程中扮演着重要的角色[32]。近年来,PERK信号通路在激素性股骨头缺血坏死中的研究正日渐增多。 第二条通路是IRE1α通路。内质网应激发生时,IRE1α与葡萄糖调节蛋白78分离,自体发生磷酸化,激活自身RNA酶的活性[33]。IRE1α激活主要有3个作用,首先,二聚化的IRE1剪切了X盒结合蛋白1 mRNA,导致其翻译为X盒结合蛋白1(一种有效的转录因子)[22,34];X盒结合蛋白1可以促进葡萄糖调节蛋白78和内质网相关降解因子的转录,重新折叠或降解错误折叠蛋白[22,29];其次,二聚化的IRE1α通过切割将被翻译成内质网的mRNA来阻止新蛋白质的翻译[29];第三,IRE1α二聚体暴露了TRAF2的结合位点,激活了ASK1,活化的ASK1激活其下游信号分子c-Jun N末端激酶,导致细胞凋亡[22,35]。 第三条通路是激活转录因子6信号通路。激活转录因子6蛋白具有高尔基体定位信号,内质网应激时,葡萄糖调节蛋白78与激活转录因子6解离,并将激活转录因子6转移到高尔基体,在那里激活转录因子6被Site-1蛋白酶和Site-2蛋白酶切割[24]。在这种切割后,激活转录因子6从高尔基体中释放出来,移动到细胞核,在那里它充当转录因子,上调内质网伴侣蛋白,促进蛋白质折叠[22],还诱导增强子结合蛋白同源蛋白等凋亡因子的表达[36],从而触发凋亡,恢复内质网稳态。 研究表明,糖皮质激素可诱导内质网中未折叠或错误折叠的蛋白积聚,引起内质网应激[37];而当内质网应激不能及时修复时,内质网一方面可通过启动内质网特有的凋亡途径促使细胞凋亡[38];另一方面可通过激活自噬致使细胞死亡[39]。近年研究结果显示,内质网应激介导的细胞自噬及凋亡与许多肿瘤的发生发展和治疗有关[40],可见内质网应激是自噬与凋亡相互调控的重要途径。 2.3 激素性股骨头缺血坏死与内质网应激 激素性股骨头缺血坏死与内质网应激的具体联系仍无定论,由于激素会引起股骨头组织的缺血缺氧[41-42],而缺血、缺氧可作为细胞发生内质网应激的应激源[43-44],目前研究认为,内质网应激与激素性股骨头缺血坏死的发病机制有直接或间接的联系,主要包括内质网应激引起的骨细胞自噬与凋亡、内皮细胞损伤及血管损伤,从而参与到疾病的发生当中。 2.3.1 激素性股骨头缺血坏死中的细胞自噬与内质网应激 激素性股骨头缺血性坏死是由于骨细胞和成骨细胞凋亡,导致骨小梁减少,骨小梁在骨重下骨折,股骨头重建修复延迟导致股骨头塌陷[45-47],这一机制的核心是骨脆性增加和骨量丢失。破骨细胞是骨再吸收细胞,破骨细胞的过度活跃会导致骨丢失和骨质疏松,而自噬与破骨细胞关系密切。自噬所必需的蛋白质,包括自噬相关蛋白5、自噬相关蛋白7、自噬相关蛋白4B和自噬相关蛋白LC3,在破骨细胞“褶边边界”的产生和破骨细胞的分泌功能以及体外、体内的骨吸收中发挥重要作用[48-49]。FIP200是ULKs-Atg13-FIP200复合体的重要组成部分,在哺乳动物雷帕霉素靶点下游作用,参与自噬的形成,这是诱导哺乳动物细胞自噬的必要条件[50]。此外,LIU等[51]发现FIP200的缺失会抑制成骨细胞自噬,导致骨丢失和骨强度降低,这说明自噬在成骨细胞分化和骨发育中发挥了积极作用。破骨细胞通过骨相关质膜与溶酶体分泌物融合产生的褶边边界吸收骨[52],自噬蛋白自噬相关蛋白5、自噬相关蛋白7和自噬相关蛋白4B/LC3可以调节溶酶体和吞噬体的融合[53];脂质体LC3在破骨细胞的褶边边界定位依赖于自噬相关蛋白5,自噬相关蛋白5-自噬相关蛋白12结合体和自噬相关蛋白4B是高效溶酶体定位和骨吸收的必要条件[49];自噬和细胞凋亡参与了激素性股骨头缺血坏死的发病机制[54]。 越来越多的数据表明,内质网应激可以触发自 噬[55-56],在不同类型的细胞中自噬可以促进细胞存活或细胞死亡[57-58]。GAO等[59]通过对地塞米松处理的人内皮细胞进行研究发现,糖皮质激素激活了未折叠蛋白反应下游IRE1α- X 盒结合蛋白1的信号通路,从而引起细胞自噬,在内皮细胞中发挥抗凋亡和促增殖作用。相反,LIU等[60]通过在地塞米松处理的Mc3T3-E1成骨样细胞研究中发现,糖皮质激素通过引起内质网应激和增加自噬导致成骨细胞的凋亡;但自噬诱导也与内质网应激的产生有关。 综上所述,糖皮质激素可以引起内质网应激,进而引发自噬,但是在激素性股骨头缺血坏死中,内质网应激与自噬的互相关系以及自噬具体起到保护还是不利作用,自噬与凋亡的关系现在还没有明确,仍需要进一步研究。 2.3.2 激素性股骨头缺血坏死中的细胞凋亡与内质网应激 目前,大多数学者认为激素性股骨头缺血坏死的发生机制与缺血诱导的细胞凋亡是分不开的[4,61]。细胞凋亡途径有线粒体途径和内质网途径,内质网途径也激活线粒体途径[62]。适度的内质网应激会诱导未折叠蛋白反应来适当保护细胞,而过度和持续的内质网应激可能通过激活增强子结合蛋白同源蛋白、半胱氨酸蛋白酶12和c-Jun N末端激酶通路而导致细胞凋亡[8,63]。 大剂量糖皮质激素治疗增加了细胞凋亡,糖皮质激素诱导的细胞凋亡是由于激素对骨细胞的直接作用[64]。最近,一些学者将糖皮质激素诱导细胞凋亡的机制着眼于内质网应激的途径上[27]。SATO等[10]通过抑制真核翻译起始因子2α去磷酸化来对抗内质网应激,从而在体内外阻止了成骨细胞和骨细胞的凋亡以及糖皮质激素诱导的成骨细胞功能下降。同样的,Liu等[7]在手术诱导的激素性股骨头缺血坏死大鼠模型研究中发现,Salubrinal,一种选择性真核翻译起始因子2α去磷酸化抑制剂,可以促进激素性股骨头缺血坏死中的成骨细胞分化,并且抑制破骨细胞生成。TAO等[65]通过在地塞米松处理的体外细胞模型和甲基强的松龙处理的体内大鼠模型中研究发现,富血小板血浆外泌体通过Akt/Bad/Bcl-2信号通路促进内质网应激下Bcl-2的表达,从而阻止糖皮质激素诱导的激素性股骨头缺血坏死中骨细胞和内皮细胞的凋亡。此外,YANG等[66]检测了地塞米松处理的MC3T3-E1成骨细胞中葡萄糖调节蛋白78、增强子结合蛋白同源蛋白和磷酸化真核翻译起始因子2a的表达水平,糖皮质激素可能通过增强内质网应激促进成骨细胞凋亡,并且4-苯基丁酸可以抑制内质网应激进而减少糖皮质激素诱导的成骨细胞凋亡。 综上所述,激素性股骨头缺血坏死中,内质网应激不仅调控骨细胞[67]、成骨细胞及内皮细胞凋亡,还促进软骨细胞的凋亡[68],但具体调节机制还有待进一步研究。 2.3.3 内质网应激与血管损伤 糖皮质激素诱导股骨头坏死的两种主要学说是细胞凋亡和缺血[69]。传统理论认为缺血是主要致病因素,因为激素性股骨头缺血坏死的最终共同途径是骨血供中断[70-71]。一些学者也认为血管损伤才是激素性股骨头坏死的主要原因[2,72],而之后表现的病理变化仅是缺血后导致的继发性损伤[73]。 Liu等[7]研究表明,缺血是内质网应激的诱导者,而过度的内质网应激诱导破骨细胞生成并抑制血管生成。高彦淳[74]在激素性股骨头缺血坏死的早期发现,血管损伤中发生了内皮细胞凋亡,其发生机制可能与内质网应激下的PERK信号通路激活有关。刘大全[75]的体内、外实验结果表明,真核翻译起始因子2α去磷酸化抑制剂可以改善坏死股骨头中的血管重建,促进血管生成,通过上调磷酸化真核翻译起始因子2α、激活转录因子4和血管内皮生长因子的表达水平来缓解内质网应激。 糖皮质激素可直接导致股骨头组织中纤溶功能低下,间接导致内皮细胞功能障碍和损伤。血管内皮细胞的凋亡、脂质代谢和血小板的活化导致集体高凝状态,使股骨头缺血,最终导致股骨头坏死[76]。而上述结果表明,内质网应激参与其中的病理变化,与激素性股骨头中的内皮细胞凋亡和血管损伤有一定的联系。 "
[1] ZHANG YL, YIN JH, DING H, et al. Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats. Int J Biol Sci. 2016; 12(4):347-358. [2] ZHANG Y, YIN J, DING H, et al. Vitamin K2 Ameliorates Damage of Blood Vessels by Glucocorticoid: a Potential Mechanism for Its Protective Effects in Glucocorticoid-induced Osteonecrosis of the Femoral Head in a Rat Model. Int J Biol Sci. 2016;12(7):776-785. [3] HAO C, YANG S, XU W, et al. MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3. Sci Rep. 2016;6:22599. [4] YOUM YS, LEE SY, LEE SH. Apoptosis in the osteonecrosis of the femoral head. Clin Orthop Surg. 2010;2(4):250-255. [5] ZHU Y, ZHOU J, AO R, et al. A-769662 protects osteoblasts from hydrogen dioxide-induced apoptosis through activating of AMP-activated protein kinase (AMPK). Int J Mol Sci. 2014;15(6): 11190-11203. [6] WEINSTEIN RS, WAN C, LIU Q, et al. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell. 2010;9(2):147-161. [7] LIU D, ZHANG Y, LI X, et al. eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress. Sci Rep. 2017; 7(1):5062. [8] HUGHES A, OXFORD AE, TAWARA K, et al. Endoplasmic reticulum stress and unfolded protein response in cartilage pathophysiology; contributing factors to apoptosis and osteoarthritis. Int J Mol Sci. 2017; 18(3):665. [9] CHUNG CY, KHURANA V, AULUCK PK, et al. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science. 2013;342(6161):983-987. [10] SATO AY, TU X, MCANDREWS KA, et al. Prevention of glucocorticoid induced-apoptosis of osteoblasts and osteocytes by protecting against endoplasmic reticulum (ER) stress in vitro and in vivo in female mice. Bone. 2015;73:60-68. [11] LISSE TS, THIELE F, FUCHS H, et al. ER stress-mediated apoptosis in a new mouse model of osteogenesis imperfecta. PLoS Genet. 2008;4(2): e7. [12] BINET F, SAPIEHA P. ER Stress and Angiogenesis. Cell Metab. 2015; 22(4):560-575. [13] PARK S H, BLACKSTONE C. Further assembly required: construction and dynamics of the endoplasmic reticulum network. EMBO Rep. 2010; 11(7):515-521. [14] VAN MEER G, VOELKER DR, FEIGENSON GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9(2): 112-124. [15] FEWELL SW, TRAVERS KJ, WEISSMAN JS, et al. The action of molecular chaperones in the early secretory pathway. Annu Rev Genet. 2001;35: 149-191. [16] ELLGAARD L, HELENIUS A. Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol. 2003;4(3):181-191. [17] BERRIDGE MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 2002;32(5-6):235-249. [18] ARAKI K, NAGATA K. Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol. 2011;3(11):a007526. [19] BERTOLOTTI A, ZHANG Y, HENDERSHOT LM, et al. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000;2(6):326-232. [20] LEE AS. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001;26(8):504-510. [21] ELETTO D, DERSH D, ARGON Y. GRP94 in ER quality control and stress responses. Semin Cell Dev Biol. 2010;21(5):479-485. [22] XU Y, GUO M, JIANG W, et al. Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury. Ren Fail. 2016;38(5):831-837. [23] WANG M, KAUFMAN RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature. 2016;529(7586): 326-335. [24] DICKHOUT JG, CARLISLE RE, AUSTIN RC. Interrelationship between cardiac hypertrophy, heart failure, and chronic kidney disease: endoplasmic reticulum stress as a mediator of pathogenesis. Circ Res. 2011;108(5):629-642. [25] DICKHOUT JG, KREPINSKY JC. Endoplasmic reticulum stress and renal disease. Antioxid Redox Signal. 2009;11(9):2341-2352. [26] GALLOT YS, BOHNERT KR, STRAUGHN AR, et al. PERK regulates skeletal muscle mass and contractile function in adult mice. FASEB J. 2019; 33(2):1946-1962. [27] ROZPEDEK W, PYTEL D, MUCHA B, et al. The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress. Curr Mol Med. 2016;16(6):533-544. [28] KANG X, YANG W, WANG R, et al. Sirtuin-1 (SIRT1) stimulates growth-plate chondrogenesis by attenuating the PERK-eIF-2α-CHOP pathway in the unfolded protein response. J Biol Chem. 2018;293(22):8614-8625. [29] AMIN-WETZEL N, SAUNDERS RA, KAMPHUIS MJ, et al. A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response. Cell. 2017;171(7):1625-1637.e13. [30] SALAROGLIO IC, PANADA E, MOISO E, et al. PERK induces resistance to cell death elicited by endoplasmic reticulum stress and chemotherapy. Mol Cancer. 2017;16(1):91. [31] TANG JY, JIN P, HE Q, et al. Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6, IRE1α and PERK signaling activation. Mol Cell Biochem. 2017;424(1-2):111-122. [32] HUGHES D, MALLUCCI GR. The unfolded protein response in neurodegenerative disorders - therapeutic modulation of the PERK pathway. FEBS J. 2019;286(2):342-355. [33] JIANG D, TAM AB, ALAGAPPAN M, et al. Acridine Derivatives as Inhibitors of the IRE1α-XBP1 Pathway Are Cytotoxic to Human Multiple Myeloma. Mol Cancer Ther. 2016;15(9):2055-2065. [34] ROJAS-RIVERA D, RODRIGUEZ DA, SEPULVEDA D, et al. ER stress sensing mechanism: Putting off the brake on UPR transducers. Oncotarget. 2018;9(28):19461-19462. [35] GUO Y, LIN D, ZHANG M, et al. CLDN6-induced apoptosis via regulating ASK1-p38/JNK signaling in breast cancer MCF-7 cells. Int J Oncol. 2016; 48(6):2435-2444. [36] SUN L, ZHANG SS, LU SJ, et al. Site-1 protease cleavage site is important for the ER stress-induced activation of membrane-associated transcription factor bZIP28 in Arabidopsis. Sci China Life Sci. 2015; 58(3):270-275. [37] ZHOU T, LV X, GUO X, et al. RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis. Oncol Rep. 2015;33(6):3006-3014. [38] HUANG Y, LENG TD, INOUE K, et al. TRPM7 channels play a role in high glucose-induced endoplasmic reticulum stress and neuronal cell apoptosis. J Biol Chem. 2018;293(37):14393-14406. [39] CHEN N, DAI L, JIANG Y, et al. Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy. Brain Dev. 2016;38(5):507-515. [40] LI H, CHEN H, LI R, et al. Cucurbitacin I induces cancer cell death through the endoplasmic reticulum stress pathway. J Cell Biochem. 2018 Sep 11. doi: 10.1002/jcb.27570. [41] ZHAO ZQ, BAI R, LIU WL, et al. Roles of oxidative DNA damage of bone marrow hematopoietic cells in steroid-induced avascular necrosis of femoral head. Genet Mol Res. 2016;15(1). doi: 10.4238/gmr.15017706. [42] BAI R, NA Y, LIU W, et al. Quantitative assessment of ABCB1 polymorphisms and non-traumatic osteonecrosis of the femur head risk. 2016;9:21542-21548. [43] XIE Y, YE S, ZHANG J, et al. Protective effect of mild endoplasmic reticulum stress on radiation-induced bystander effects in hepatocyte cells. Sci Rep. 2016;6:38832. [44] KEMTER E, FRÖHLICH T, ARNOLD GJ, et al. Mitochondrial Dysregulation Secondary to Endoplasmic Reticulum Stress in Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD (ADTKD-UMOD). Sci Rep. 2017;7:42970. [45] SHI J, WANG L, ZHANG H, et al. Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy. Bone. 2015;79:222-232. [46] HE M, WANG J, WANG G, et al. Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis. Mol Med Rep. 2016; 14(2):1054-1060. [47] ZOU W, YANG S, ZHANG T, et al. Hypoxia enhances glucocorticoid-induced apoptosis and cell cycle arrest via the PI3K/Akt signaling pathway in osteoblastic cells. J Bone Miner Metab. 2015;33(6): 615-624. [48] STENBECK G, COXON FP. Role of vesicular trafficking in skeletal dynamics. Curr Opin Pharmacol. 2014;16:7-14. [49] DESELM CJ, MILLER BC, ZOU W, et al. Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev Cell. 2011; 21(5):966-974. [50] HARA T, TAKAMURA A, KISHI C, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181(3):497-510. [51] LIU F, FANG F, YUAN H, et al. Suppression of autophagy by FIP200 deletion leads to osteopenia in mice through the inhibition of osteoblast terminal differentiation. J Bone Miner Res. 2013;28(11): 2414-2430. [52] STENBECK G. Formation and function of the ruffled border in osteoclasts. Semin Cell Dev Biol. 2002;13(4):285-292. [53] LEE HK, MATTEI LM, STEINBERG BE, et al. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity. 2010;32(2): 227-239. [54] LUO P, GAO F, HAN J, et al. The role of autophagy in steroid necrosis of the femoral head: a comprehensive research review. Int Orthop. 2018; 42(7):1747-1753. [55] LIN CJ, LEE CC, SHIH YL, et al. Inhibition of mitochondria- and endoplasmic reticulum stress-mediated autophagy augments temozolomide-induced apoptosis in glioma cells. PLoS One. 2012;7(6): e38706. [56] CYBULSKY AV. The intersecting roles of endoplasmic reticulum stress, ubiquitin- proteasome system, and autophagy in the pathogenesis of proteinuric kidney disease. Kidney Int. 2013;84(1):25-33. [57] EL ZAOUI I, BEHAR-COHEN F, TORRIGLIA A. Glucocorticoids exert direct toxicity on microvasculature: analysis of cell death mechanisms. Toxicol Sci. 2015;143(2):441-453. [58] YU QS, GUO WS, CHENG LM, et al. Glucocorticoids Significantly Influence the Transcriptome of Bone Microvascular Endothelial Cells of Human Femoral Head. Chin Med J (Engl). 2015;128(14):1956-1963. [59] GAO Y, ZHU H, YANG F, et al. Glucocorticoid-activated IRE1α/XBP-1s signaling: an autophagy-associated protective pathway against endotheliocyte damage. Am J Physiol Cell Physiol. 2018;315(3): C300-C309. [60] LIU W, ZHAO Z, NA Y, et al. Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells. Int J Mol Med. 2018;41(4): 2028-2036. [61] WEINSTEIN RS, NICHOLAS RW, MANOLAGAS SC. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J Clin Endocrinol Metab. 2000;85(8):2907-2912. [62] BOYA P, COHEN I, ZAMZAMI N, et al. Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. Cell Death Differ. 2002;9(4):465-467. [63] ALMADA M, FONSECA BM, AMARAL C, et al. Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis. Apoptosis. 2017;22(6):816-826. [64] PLOTKIN LI, MANOLAGAS SC, BELLIDO T. Glucocorticoids induce osteocyte apoptosis by blocking focal adhesion kinase-mediated survival. Evidence for inside-out signaling leading to anoikis. J Biol Chem. 2007;282(33):24120-24130. [65] TAO SC, YUAN T, RUI BY, et al. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics. 2017;7(3):733-750. [66] YANG J, WU Q, LV J, et al. 4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress. J Bone Miner Metab. 2017;35(4):366-374. [67] YIN J, HAN L, CONG W. Alpinumisoflavone rescues glucocorticoid-induced apoptosis of osteocytes via suppressing Nox2-dependent ROS generation. Pharmacol Rep. 2018;70(2):270-276. [68] ZHANG M, LI S, PANG K, et al. Endoplasmic reticulum stress affected chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers. Poult Sci. 2019;98(3):1111-1120. [69] WEINSTEIN RS, CHEN JR, POWERS CC, et al. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J Clin Invest. 2002;109(8):1041-1048. [70] WEI B, WEI W, ZHAO B, et al. Long non-coding RNA HOTAIR inhibits miR-17-5p to regulate osteogenic differentiation and proliferation in non-traumatic osteonecrosis of femoral head. PLoS One. 2017;12(2): e0169097. [71] YU Z, FAN L, LI J, et al. Lithium prevents rat steroid-related osteonecrosis of the femoral head by β-catenin activation. Endocrine. 2016;52(2):380-390. [72] LI J, FAN L, YU Z, et al. The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads. Exp Biol Med (Maywood). 2015;240(2):273-280. [73] BRANDI ML, COLLIN-OSDOBY P. Vascular biology and the skeleton. J Bone Miner Res. 2006;21(2):183-192. [74] 高彦淳. 糖皮质激素引起的内质网应激与内皮细胞凋亡[D]. 上海:上海交通大学, 2018. [75] 刘大全. 调节干细胞分化和内质网应激治疗股骨头坏死的机制研究[D]. 天津:天津医科大学, 2017. [76] ZHANG Q, L V J, JIN L. Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head. J Int Med Res. 2018;46(6): 2141-2148. [77] NARAYANAN A, KHANCHANDANI P, BORKAR RM, et al. Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization. Sci Rep. 2017;7(1):10721. [78] KUBO T, UESHIMA K, SAITO M, et al. Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan. J Orthop Sci. 2016;21(4):407-413. [79] ADILI A, TROUSDALE RT. Femoral head resurfacing for the treatment of osteonecrosis in the young patient. Clin Orthop Relat Res. 2003;(417): 93-101. [80] IURLARO R, MUÑOZ-PINEDO C. Cell death induced by endoplasmic reticulum stress. FEBS J. 2016;283(14):2640-2652. [81] CUBILLOS-RUIZ JR, MOHAMED E, RODRIGUEZ PC. Unfolding anti-tumor immunity: ER stress responses sculpt tolerogenic myeloid cells in cancer. J Immunother Cancer. 2017;5:5. |
[1] | Wang Yue, Wang Xinjun, Yuan Yinpeng, Wang Yuze. Mechanism of DAIa2GIP inhibiting mitochondrial apoptosis in chondrocytes [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1652-1657. |
[2] | Zhao Ning, Yu Hongdan, Feng Zhen, Ding Jiayuan, Liu Xuezheng. Salidroside inhibits apoptosis of retinal Müller cells induced by high glucose in rats [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1664-1669. |
[3] | Cao Haixin, Wang Xiaomei . Aerobic exercise protects the rat brain against senile dementia induced by amyloid beta protein 1-42 [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1675-1681. |
[4] | Shui Xiaoping, Li Chunying, Cao Yanxia, Su Quansheng. Effects of aerobic and resistance exercises on endoplasmic reticulum stress-related proteins in diabetic peripheral neuropathy rats [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(11): 1693-1698. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||