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中华口腔医学研究杂志(电子版) ›› 2021, Vol. 15 ›› Issue (05) : 309 -313. doi: 10.3877/cma.j.issn.1674-1366.2021.05.010

综述

内质网应激在骨代谢及其稳态中的作用
林锐钿1, 李子涵1, 古丽莎1,()   
  1. 1. 中山大学附属口腔医院,光华口腔医学院,广东省口腔医学重点实验室,广州 510055
  • 收稿日期:2020-11-16 出版日期:2021-10-01
  • 通信作者: 古丽莎

Endoplasmic reticulum stress in skeletal development and bone homostasis

Ruitian Lin1, Zihan Li1, Lisha Gu1,()   

  1. 1. Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2020-11-16 Published:2021-10-01
  • Corresponding author: Lisha Gu
  • Supported by:
    National Natural Science Foundation of China(81873712); Science and Technology Planning Project of Guangzhou(201904010057)
引用本文:

林锐钿, 李子涵, 古丽莎. 内质网应激在骨代谢及其稳态中的作用[J/OL]. 中华口腔医学研究杂志(电子版), 2021, 15(05): 309-313.

Ruitian Lin, Zihan Li, Lisha Gu. Endoplasmic reticulum stress in skeletal development and bone homostasis[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2021, 15(05): 309-313.

骨稳态是破骨细胞和成骨细胞共同作用的过程。骨组织中存在大量的细胞外基质蛋白。在蛋白合成过程中,未折叠及错误折叠蛋白增多导致内质网应激,诱发肌醇必需酶1α(IRE1α)、内质网膜蛋白激酶(PERK)和活化转录因子6(ATF6)家族介导的非折叠蛋白应答。当过度应激时将造成软骨发育不良、骨关节炎和牙周炎骨吸收等疾病。本文就近年内质网应激在骨代谢中作用的研究进展做一综述,有助于进一步了解内质网应激在骨代谢及治疗相关疾病中的作用及意义。

Bone homeostasis is a process of interaction between osteoclasts and osteoblasts, with abundant extracellular matrix proteins existing in bone tissue. During protein synthesis, the increase of unfolded and misfolded proteins lead to endoplasmic reticulum stress, which induce the unfolded protein responses mediated by IRE1α, PERK and ATF6 family. Excessive stress leads to chondrodysplasia, osteoarthritis and periodontitis bone resorption. This review focuses on the role of endoplasmic reticulum stress in bone metabolism and it is of great significance for our further understanding of bone metabolism and treatment of related diseases.

[1]
Rapoport TA, Li L, Park E. Structural and mechanistic insights into protein translocation[J]. Annu Rev Cell Dev Biol201733:369-390. DOI:10.1146/annurev-cellbio-100616-060439.
[2]
Xu C, Bailly-Maitre B, Reed JC. Endoplasmic reticulum stress:Cell life and death decisions[J]. J Clin Invest2005115(10):2656-2664. DOI:10.1172/jci26373.
[3]
Chen Y, Yang H, Miao J,et al. Roles of the endoplasmic reticulum stress transducer OASIS in ossification of the posterior longitudinal ligament[J]. Clin Spine Surg201730(1):E19-E24. DOI:10.1097/BSD.0b013e3182908c21.
[4]
Kim JH, Kim K, Kim I,et al. Endoplasmic reticulum-bound transcription factor CREBH stimulates RANKL-induced osteoclastogenesis[J]. J Immunol2018200(5):1661-1670. DOI:10.4049/jimmunol.1701036.
[5]
Briggs MD, Dennis EP, Dietmar HF,et al. New developments in chondrocyte ER stress and related diseases[J]. F1000Res20209:290. DOI:10.12688/f1000research.22275.1.
[6]
Son HE, Min HY, Kim EJ,et al. Fat mass and obesity-associated (FTO)stimulates osteogenic differentiation of C3H10T1/2 cells by inducing mild endoplasmic reticulum stress via a positive feedback loop with p-AMPK[J]. Mol Cells202043(1):58-65. DOI:10.14348/molcells.2019.0136.
[7]
Hetz C, Zhang K, Kaufman RJ. Mechanisms,regulation and functions of the unfolded protein response[J]. Nat Rev Mol Cell Biol202021(8):421-438. DOI:10.1038/s41580-020-0250-z.
[8]
Kular J, Tickner J, Chim SM,et al. An overview of the regulation of bone remodelling at the cellular level[J]. Clin Biochem201245(12):863-873. DOI:10.1016/j.clinbiochem.2012.03.021.
[9]
Choi Y, Lee EG, Jeong JH,et al. 4-Phenylbutyric acid,a potent endoplasmic reticulum stress inhibitor,attenuates the severity of collagen-induced arthritis in mice via inhibition of proliferation and inflammatory responses of synovial fibroblasts[J]. Kaohsiung J Med Sci202137(7):604-615. DOI:10.1002/kjm2.12376.
[10]
Yamada H, Nakajima T, Domon H,et al. Endoplasmic reticulum stress response and bone loss in experimental periodontitis in mice[J]. J Periodontal Res201550(4):500-508. DOI:10.1111/jre.12232.
[11]
Tirasophon W, Welihinda AA, Kaufman RJ. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease(Ire1p)in mammalian cells[J]. Genes Dev199812(12):1812-1824. DOI:10.1101/gad.12.12.1812.
[12]
Calfon M, Zeng HQ, Urano F,et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA[J]. Nature2002415(6867):92-96. DOI:10.1038/415092a.
[13]
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response[J]. Nat Rev Mol Cell Biol20078(7):519-529. DOI:10.1038/nrm2199.
[14]
黄媚,陈熙,邹军. ATF4在内质网应激调控成骨分化中的作用[J].中国生物化学与分子生物学报202036(1):29-35. DOI:10.13865/j.cnki.cjbmb.2019.11.1165.
[15]
Novoa I, Zeng H, Harding HP,et al. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha[J]. J Cell Biol2001153(5):1011-1022. DOI:10.1083/jcb.153.5.1011.
[16]
Marciniak SJ, Yun CY, Oyadomari S,et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum[J]. Genes Dev200418(24):3066-3077. DOI:10.1101/gad.1250704.
[17]
Chen X, Shen J, Prywes R. The luminal domain of ATF6 senses endoplasmic reticulum(ER)stress and causes translocation of ATF6 from the ER to the Golgi[J]. J Biol Chem2002277(15):13045-13052. DOI:10.1074/jbc.M110636200.
[18]
Haze K, Yoshida H, Yanagi H,et al. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress[J]. Mol Biol Cell199910(11):3787-3799. DOI:DOI 10.1091/mbc.10.11.3787.
[19]
Ye J, Rawson RB, Komuro R,et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs[J]. Mol Cell20006(6):1355-1364. DOI:10.1016/S1097-2765(00)00133-7.
[20]
Iyer S, Melendez-Suchi C, Han L,et al. Elevation of the unfolded protein response increases RANKL expression[J]. FASEB Bioadv20202(4):207-218. DOI:10.1096/fba.2019-00032.
[21]
Taipaleenmäki H, Bjerre Hokland L, Chen L,et al. Micro-RNAs:Targets for enhancing osteoblast differentiation and bone formation[J]. Eur J Endocrinol2012166(3):359-371. DOI:10.1530/eje-11-0646.
[22]
Rutkovskiy A, Stenslokken KO, Vaage IJ. Osteoblast differentiation at a glance[J]. Med Sci Monit Basic Res201622:95-106. DOI:10.12659/Msmbr.901142.
[23]
Yang SY, Wei FL, Hu LH,et al. PERK-eIF2α-ATF4 pathway mediated by endoplasmic reticulum stress response is involved in osteodifferentiation of human periodontal ligament cells under cyclic mechanical force[J]. Cell Signal201628(8):880-886. DOI:10.1016/j.cellsig.2016.04.003.
[24]
李莉芬,文扬,江龙,等.内质网应激在牙周膜细胞成骨分化中的表达[J].上海口腔医学201726(6):577-581. DOI:10.19439/j.sjos.2017.06.001.
[25]
Xue P, Li B, An Y,et al. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation[J]. Cell Death Differ201623(11):1862-1872. DOI:10.1038/cdd.2016.74.
[26]
Shirakawa K, Maeda S, Gotoh T,et al. CCAAT/enhancer-binding protein homologous protein(CHOP)regulates osteoblast differentiation[J]. Mol Cell Biol200626(16):6105-6016. DOI:10.1128/mcb.02429-05.
[27]
Pereira RC, Stadmeyer L, Marciniak SJ,et al. C/EBP homologous protein is necessary for normal osteoblastic function[J]. J Cell Biochem200697(3):633-640. DOI:10.1002/jcb.20660.
[28]
Wu CT, Chen YW, Su YH,et al. Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia[J]. J Orthop Res201937(4):942-947. DOI:10.1002/jor.24264.
[29]
Jang WG, Kim EJ, Kim DK,et al. BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription[J]. J Biol Chem2012287(2):905-915. DOI:10.1074/jbc.M111.253187.
[30]
Jang WG, Jeong BC, Kim EJ,et al. Cyclic AMP response element-binding protein H(CREBH)mediates the inhibitory actions of tumor necrosis factor alpha in osteoblast differentiation by stimulating smad1 degradation[J]. J Biol Chem2015290(21):13556-13566. DOI:10.1074/jbc.M114.587923.
[31]
Murakami T, Saito A, Hino S,et al. Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation[J]. Nat Cell Biol200911(10):1205-1211. DOI:10.1038/ncb1963.
[32]
Piróg KA, Dennis EP, Hartley CL,et al. XBP1 signalling is essential for alleviating mutant protein aggregation in ER-stress related skeletal disease[J]. PLoS Genet201915(7):e1008215. DOI:10.1371/journal.pgen.1008215.
[33]
Huang Z, Zhou M, Wang Q,et al. Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress[J]. Arch Oral Biol201784:125-132. DOI:10.1016/j.archoralbio.2017.09.021.
[34]
Zhu M, Zhou S, Huang Z,et al. Ca2+-dependent endoplasmic reticulum stress regulates mechanical stress-mediated cartilage thinning[J]. J Dent Res201695(8):889-896. DOI:10.1177/0022034516640206.
[35]
Wang C, Tan Z, Niu B,et al. Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia[J]. Elife20187:e37673. DOI:10.7554/eLife.37673.
[36]
Shi L, Shi G, Li T,et al. The endoplasmic reticulum stress response participates in connexin 43-mediated ossification of the posterior longitudinal ligament[J]. Am J Transl Res201911(7):4113-4125.
[37]
Cameron TL, Bell KM, Gresshoff IL,et al. XBP1-independent UPR pathways suppress C/EBP-β mediated chondrocyte differentiation in ER-stress related skeletal disease[J]. PLoS Genet201511(9):e1005505. DOI:10.1371/journal.pgen.1005505.
[38]
Cameron TL, Gresshoff IL, Bell KM,et al. Cartilage-specific ablation of XBP1 signaling in mouse results in a chondrodysplasia characterized by reduced chondrocyte proliferation and delayed cartilage maturation and mineralization[J]. Osteoarthritis Cartilage201523(4):661-670. DOI:10.1016/j.joca.2015.01.001.
[39]
Zhang Y, Jiang P, Li W,et al. Calcineurin/NFAT signaling pathway mediates titanium particle-induced inflammation and osteoclast formation by inhibiting RANKL and M-CSF in vitro[J]. Mol Med Rep201716(6):8223-8230. DOI:10.3892/mmr.2017.7670.
[40]
Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function[J]. Nat Rev Genet20034(8):638-649. DOI:10.1038/nrg1122.
[41]
Nakashima T, Hayashi M, Takayanagi H. New insights into osteoclastogenic signaling mechanisms[J]. Trends Endocrinol Metab201223(11):582-590. DOI:10.1016/j.tem.2012.05.005.
[42]
Zhang L, Bao D, Li P,et al. Particle-induced SIRT1 downregulation promotes osteoclastogenesis and osteolysis through ER stress regulation[J]. Biomed Pharmacother2018104:300-306. DOI:10.1016/j.biopha.2018.05.030.
[43]
Lee WS, Jeong JH, Lee EG,et al. Tacrolimus regulates endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation:In vitro and collagen-induced arthritis mouse model[J]. Cell Biol Int201842(4):393-402. DOI:10.1002/cbin.10861.
[44]
Wang Z, Liu N, Zhou G,et al. Expression of XBP1s in fibroblasts is critical for TiAl6V4 particle-induced RANKL expression and osteolysis[J]. J Orthop Res201735(4):752-759. DOI:10.1002/jor.23056.
[45]
Tohmonda T, Yoda M, Iwawaki T,et al. IRE1α/XBP1-mediated branch of the unfolded protein response regulates osteoclastogenesis[J]. J Clin Invest2015125(8):3269-3279. DOI:10.1172/jci76765.
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