OpenLB
Open Library of Bioscience
Advanced Search
Frontiers in cell and developmental biology
2021;9 819139.

Endoplasmic Reticulum Stress: An Emerging Therapeutic Target for Intervertebral Disc Degeneration.

Dong Wang, Xin He, Chao Zheng, Chengzhe Wang, Pandi Peng, Chu Gao, Xiaolong Xu, Yachao Ma, Mei Liu, Liu Yang, Zhuojing Luo
Author Information
  1. Dong Wang: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  2. Xin He: Pharmacy Department, Air Force Hospital of Eastern Theater Command, Nanjing, China.
  3. Chao Zheng: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  4. Chengzhe Wang: Rehabilitation Department, Dongchangfu Traditional Chinese Medicine Hospital, Liaocheng, China.
  5. Pandi Peng: Institute of Flexible Electronics, Northwestern Polytechnical University, Xi'an, China.
  6. Chu Gao: Medical Research Institute, Northwestern Polytechnical University, Xi'an, China.
  7. Xiaolong Xu: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  8. Yachao Ma: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  9. Mei Liu: Pharmacy Department, Air Force Hospital of Eastern Theater Command, Nanjing, China.
  10. Liu Yang: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
  11. Zhuojing Luo: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
PMID: 35178406 DOI: 10.3389/fcell.2021.819139

Abstract

Low back pain (LBP) is a global health issue. Intervertebral disc degeneration (IDD) is a major cause of LBP. Although the explicit mechanisms underpinning IDD are unclear, endoplasmic reticulum (ER) stress caused by aberrant unfolded or misfolded proteins may be involved. The accumulation of unfolded/misfolded proteins may result in reduced protein synthesis and promote aberrant protein degradation to recover ER function, a response termed the unfolded protein response. A growing body of literature has demonstrated the potential relationships between ER stress and the pathogenesis of IDD, indicating some promising therapeutic targets. In this review, we summarize the current knowledge regarding the impact of ER stress on the process of IDD, as well as some potential therapeutic strategies for alleviating disc degeneration by targeting different pathways to inhibit ER stress. This review will facilitate understanding the pathogenesis and progress of IDD and highlights potential therapeutic targets for treating this condition.

Keywords

cellular homeostasis endoplasmic reticulum intervertebral disc degeneration low back pain unfolded protein response

References

  1. J Exp Med. 2012 Apr 9;209(4):871-86 [PMID: 22430489]
  2. Osteoarthritis Cartilage. 2013 Dec;21(12):2030-8 [PMID: 24120490]
  3. FEBS J. 2019 Nov;286(21):4356-4373 [PMID: 31230413]
  4. Ann Rheum Dis. 2017 Mar;76(3):576-584 [PMID: 27489225]
  5. Biores Open Access. 2018 Feb 01;7(1):2-9 [PMID: 29445584]
  6. Lancet. 2021 Dec 19;396(10267):2006-2017 [PMID: 33275908]
  7. Int J Mol Sci. 2018 Dec 07;19(12): [PMID: 30544499]
  8. Nat Commun. 2019 Mar 20;10(1):1280 [PMID: 30894532]
  9. Spine (Phila Pa 1976). 2000 Feb 15;25(4):487-92 [PMID: 10707396]
  10. Biosci Rep. 2019 Aug 7;39(8): [PMID: 31285389]
  11. Theor Biol Med Model. 2015 Nov 09;12:24 [PMID: 26552736]
  12. Nat Rev Neurol. 2017 Aug;13(8):477-491 [PMID: 28731040]
  13. Curr Rheumatol Rep. 2019 Nov 11;21(10):58 [PMID: 31712904]
  14. Cell Metab. 2009 Jul;10(1):13-26 [PMID: 19583950]
  15. Circulation. 2019 Apr 30;139(18):2085-2088 [PMID: 31034286]
  16. Cold Spring Harb Perspect Biol. 2019 Apr 1;11(4): [PMID: 30396883]
  17. J Autoimmun. 2014 May;50:59-66 [PMID: 24387801]
  18. Cell Death Differ. 2017 Jun;24(6):1100-1110 [PMID: 28452996]
  19. Ageing Res Rev. 2020 Jan;57:100997 [PMID: 31816444]
  20. Disabil Rehabil. 2021 Apr;43(7):1029-1043 [PMID: 31368371]
  21. Theranostics. 2019 Apr 12;9(8):2252-2267 [PMID: 31149042]
  22. Nat Rev Mol Cell Biol. 2020 Mar;21(3):151-166 [PMID: 32034394]
  23. EBioMedicine. 2019 Feb;40:695-709 [PMID: 30685387]
  24. J Cell Mol Med. 2019 Jan;23(1):177-193 [PMID: 30353656]
  25. Nat Rev Mol Cell Biol. 2012 Jan 18;13(2):89-102 [PMID: 22251901]
  26. J Orthop Res. 2014 Feb;32(2):253-61 [PMID: 24307209]
  27. Cell Stress Chaperones. 1996 Jun;1(2):109-15 [PMID: 9222596]
  28. DNA Cell Biol. 2018 Apr;37(4):347-358 [PMID: 29381432]
  29. Nat Cell Biol. 2013 May;15(5):481-90 [PMID: 23624402]
  30. Nat Commun. 2019 Sep 30;10(1):4443 [PMID: 31570707]
  31. Spine J. 2021 Sep;21(9):1567-1579 [PMID: 34000376]
  32. Mol Cell. 2019 Jun 6;74(5):877-890.e6 [PMID: 31023583]
  33. Nat Chem Biol. 2019 Nov;15(11):1129 [PMID: 31439938]
  34. Physiotherapy. 2020 Jun;107:224-233 [PMID: 32026824]
  35. Trends Biochem Sci. 2014 May;39(5):245-54 [PMID: 24657016]
  36. Nat Cell Biol. 2003 Dec;5(12):1051-61 [PMID: 14608362]
  37. Cell. 2019 Nov 27;179(6):1246-1248 [PMID: 31778650]
  38. Curr Pain Headache Rep. 2019 Mar 11;23(3):23 [PMID: 30854609]
  39. Nat Rev Endocrinol. 2019 Feb;15(2):73-74 [PMID: 30552380]
  40. Cell Death Dis. 2016 Oct 27;7(10):e2441 [PMID: 27787519]
  41. Exp Cell Res. 2017 Sep 15;358(2):377-389 [PMID: 28705727]
  42. J Cell Biol. 2006 Dec 4;175(5):709-14 [PMID: 17130290]
  43. Antioxid Redox Signal. 2012 May 15;16(10):1077-87 [PMID: 21854214]
  44. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7832-7 [PMID: 21521793]
  45. Cell Mol Life Sci. 2013 Jul;70(14):2425-41 [PMID: 23052213]
  46. Front Cell Dev Biol. 2020 Dec 10;8:613006 [PMID: 33363176]
  47. Trends Biochem Sci. 2015 Mar;40(3):141-8 [PMID: 25656104]
  48. Eur Spine J. 2016 Sep;25(9):2873-81 [PMID: 27480265]
  49. Biomed Pharmacother. 2017 May;89:529-535 [PMID: 28254665]
  50. Spine (Phila Pa 1976). 2000 Jul 1;25(13):1625-36 [PMID: 10870137]
  51. Lancet. 2020 Nov 14;396(10262):1560-1561 [PMID: 33189175]
  52. Oxid Med Cell Longev. 2019 Sep 9;2019:7959573 [PMID: 31583043]
  53. Theranostics. 2019 May 31;9(14):4084-4100 [PMID: 31281533]
  54. Cell Prolif. 2019 Mar;52(2):e12542 [PMID: 30430692]
  55. J Clin Invest. 2017 Oct 2;127(10):3861-3865 [PMID: 28920921]
  56. Hepatology. 2002 Sep;36(3):592-601 [PMID: 12198651]
  57. J Hepatol. 2011 Apr;54(4):795-809 [PMID: 21145844]
  58. Sci Total Environ. 2020 Apr 10;712:136480 [PMID: 31931206]
  59. Age (Dordr). 2010 Jun;32(2):161-77 [PMID: 19960285]
  60. Mol Ther Nucleic Acids. 2020 Sep 26;22:601-614 [PMID: 33230460]
  61. Evid Based Complement Alternat Med. 2018 Mar 12;2018:6719460 [PMID: 29721028]
  62. J Anat. 2012 Dec;221(6):480-96 [PMID: 22686699]
  63. Matrix Biol. 2014 Feb;34:89-95 [PMID: 24060753]
  64. Mol Cell. 2000 Nov;6(5):1099-108 [PMID: 11106749]
  65. Autophagy. 2020 Feb;16(2):271-288 [PMID: 31007149]
  66. Spine (Phila Pa 1976). 2015 Aug 1;40(15):1165-72 [PMID: 25996532]
  67. J Hepatol. 2020 Jan;72(1):183-196 [PMID: 31849347]
  68. J Clin Invest. 1996 Aug 15;98(4):996-1003 [PMID: 8770872]
  69. Cell Rep. 2013 Apr 25;3(4):1279-92 [PMID: 23583182]
  70. Eur Spine J. 2006 Aug;15 Suppl 3:S326-32 [PMID: 16736203]
  71. EMBO J. 2019 Aug 1;38(15):e100990 [PMID: 31368601]
  72. J Cell Physiol. 2019 Jul;234(7):11631-11645 [PMID: 30515797]
  73. Chest. 2020 May;157(5):1207-1220 [PMID: 31778676]
  74. Spine (Phila Pa 1976). 2020 Apr 15;45(8):E457-E464 [PMID: 31651681]
  75. Cancer Discov. 2014 Jun;4(6):702-15 [PMID: 24705811]
  76. J Biol Chem. 2002 Nov 22;277(47):44784-90 [PMID: 12237311]
  77. Nat Struct Mol Biol. 2019 Nov;26(11):1053-1062 [PMID: 31695187]
  78. Mol Cell. 2012 Nov 9;48(3):353-64 [PMID: 23022383]
  79. Ann Rheum Dis. 2018 May;77(5):770-779 [PMID: 29343508]
  80. J Biol Chem. 2019 Dec 6;294(49):18726-18741 [PMID: 31666338]
  81. EMBO J. 2019 Aug 1;38(15):e102743 [PMID: 31328793]
  82. Nat Rev Rheumatol. 2013 Jul;9(7):383 [PMID: 23712127]
  83. Nat Cell Biol. 2009 Dec;11(12):1473-80 [PMID: 19855386]
  84. Osteoarthritis Cartilage. 2015 Jul;23(7):1057-70 [PMID: 25827971]
  85. Dev Cell. 2020 Mar 23;52(6):714-730.e5 [PMID: 32109381]
  86. Spine (Phila Pa 1976). 2004 Dec 1;29(23):2700-9 [PMID: 15564919]
  87. Trends Mol Med. 2019 Jun;25(6):538-550 [PMID: 31078432]
  88. Wellcome Open Res. 2017 Oct 9;2:36 [PMID: 29062910]
  89. Bone Res. 2017 Mar 21;5:17008 [PMID: 28392965]
  90. Autophagy. 2018;14(11):1911-1927 [PMID: 30010465]
  91. Science. 2011 Nov 25;334(6059):1081-6 [PMID: 22116877]
  92. Autophagy. 2018;14(10):1726-1741 [PMID: 29962255]
  93. J Orthop Res. 2018 May;36(5):1334-1345 [PMID: 29080374]
  94. Genes Dev. 2004 Dec 15;18(24):3066-77 [PMID: 15601821]
  95. Pain Pract. 2008 Jan-Feb;8(1):18-44 [PMID: 18211591]
  96. Nature. 2018 Feb 22;554(7693):487-492 [PMID: 29469092]
  97. Apoptosis. 2011 Jun;16(6):594-605 [PMID: 21479580]
  98. Spine (Phila Pa 1976). 2017 Oct 1;42(19):1464-1471 [PMID: 28542106]
  99. J Anat. 2012 Dec;221(6):497-506 [PMID: 22881295]
  100. Science. 2019 Jul 5;365(6448): [PMID: 31273097]
  101. Nat Rev Mol Cell Biol. 2018 Feb;19(2):109-120 [PMID: 29165426]
  102. Oxid Med Cell Longev. 2021 Mar 16;2021:8810698 [PMID: 33815661]
  103. Pharmacol Res. 2017 Mar;117:357-369 [PMID: 28087442]
  104. Nature. 2016 Apr 21;532(7599):394-7 [PMID: 27007849]
  105. AJNR Am J Neuroradiol. 2015 Dec;36(12):2394-9 [PMID: 26359154]
  106. Curr Stem Cell Res Ther. 2015;10(4):285-95 [PMID: 25381758]
  107. Orthop Clin North Am. 2011 Oct;42(4):487-99, vii [PMID: 21944586]
  108. Life Sci. 2019 Jul 1;228:85-97 [PMID: 31047897]
  109. Adv Exp Med Biol. 2012;760:114-33 [PMID: 23281517]
  110. Cell Death Dis. 2017 Oct 5;8(10):e3081 [PMID: 28981117]
  111. Cell Mol Biol (Noisy-le-grand). 2018 Jul 30;64(10):61-65 [PMID: 30084796]
  112. Nat Rev Rheumatol. 2018 Apr;14(4):184 [PMID: 29467452]
  113. Oxid Med Cell Longev. 2021 Mar 24;2021:6492879 [PMID: 33833850]
  114. Mol Biol Cell. 2006 Jul;17(7):3095-107 [PMID: 16672378]
  115. Nucleic Acids Res. 2013 Sep;41(16):7683-99 [PMID: 23804767]
  116. Spine J. 2013 Mar;13(3):318-30 [PMID: 23537454]
  117. Clin Chim Acta. 2020 May;504:125-137 [PMID: 32017925]
  118. Nature. 2002 Jan 3;415(6867):92-6 [PMID: 11780124]
  119. DNA Cell Biol. 2017 Aug;36(8):627-637 [PMID: 28622016]
  120. Cell. 2019 May 16;177(5):1201-1216.e19 [PMID: 31031005]
  121. Science. 2018 Aug 3;361(6401): [PMID: 30072511]
  122. Front Immunol. 2018 Aug 17;9:1706 [PMID: 30174670]
  123. J Cell Biol. 2012 Mar 19;196(6):689-98 [PMID: 22431749]
  124. Mol Metab. 2019 Sep;27S:S60-S68 [PMID: 31500832]
  125. Lancet. 2020 Oct 17;396(10258):1204-1222 [PMID: 33069326]
  126. Cell Signal. 2016 Aug;28(8):1099-104 [PMID: 27185188]
  127. Rheumatology (Oxford). 2016 Nov;55(11):1993-2000 [PMID: 27498355]
  128. Oxid Med Cell Longev. 2021 Feb 10;2021:8884922 [PMID: 33628392]
  129. Mol Aspects Med. 2018 Oct;63:18-29 [PMID: 29559224]
  130. Int J Mol Sci. 2019 Sep 05;20(18): [PMID: 31491919]
  131. Cold Spring Harb Perspect Biol. 2013 Mar 01;5(3):a013169 [PMID: 23388626]
  132. Trends Pharmacol Sci. 2018 Jul;39(7):610-623 [PMID: 29691058]
  133. J Pineal Res. 2016 Nov;61(4):411-425 [PMID: 27555371]
Journal Article Review
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0IDDERstressproteindiscdegenerationunfoldedresponsepotentialtherapeuticbackpainLBPIntervertebralendoplasmicreticulumaberrantproteinsmaypathogenesistargetsreviewLowglobalhealthissuemajorcauseAlthoughexplicitmechanismsunderpinningunclearcausedmisfoldedinvolvedaccumulationunfolded/misfoldedresultreducedsynthesispromotedegradationrecoverfunctiontermedgrowingbodyliteraturedemonstratedrelationshipsindicatingpromisingsummarizecurrentknowledgeregardingimpactprocesswellstrategiesalleviatingtargetingdifferentpathwaysinhibitwillfacilitateunderstandingprogresshighlightstreatingconditionEndoplasmicReticulumStress:EmergingTherapeuticTargetDiscDegenerationcellularhomeostasisintervertebrallow

Similar Articles

Cited By