Endoplasmic reticulum stress in degenerative human nucleus pulposus cells

Tianyong WEN; Yue LIU; Shi CHENG; Jinwei YING; Dike RUAN

doi:10.16016/j.1000-5404.201803077

您当前的位置：

首页 >

文章列表页 >

Endoplasmic reticulum stress in degenerative human nucleus pulposus cells

Clinical Medicine | 更新时间：2026-01-09

- Endoplasmic reticulum stress in degenerative human nucleus pulposus cells
- Journal of Third Military Medical University Vol. 40, Issue 12, Pages: 1098-1103(2018)
- 作者机构：
  
  1.710032 西安，空军军医大学西京医院骨科
  2.100048 北京，海军总医院骨科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81472121);the Innovation Incubator Fund of Navy General Hospital(CXPY201402)
- DOI：10.16016/j.1000-5404.201803077
  CLC： R361.3;R394.3;R681.53
- Received：11 March 2018，
  
  Revised：2018-04-03，
  
  Published：2018-01
- 稿件说明：
移动端阅览
Tianyong WEN, Yue LIU, Shi CHENG, et al. Endoplasmic reticulum stress in degenerative human nucleus pulposus cells[J]. Journal of Third Military Medical University, 2018, 40(12): 1098-1103.
DOI：

Tianyong WEN, Yue LIU, Shi CHENG, et al. Endoplasmic reticulum stress in degenerative human nucleus pulposus cells[J]. Journal of Third Military Medical University, 2018, 40(12): 1098-1103. DOI： 10.16016/j.1000-5404.201803077.

摘要

目的

观察探讨退变与正常髓核组织中内质网应激水平的差异。

方法

获取正常和退变髓核组织共9例(均为海军总医院骨科2016年1月至2017年6月期间住院手术患者)，取组织及分离培养髓核细胞，通过透射电镜观察内质网形态、免疫组化法对髓核组织中葡萄糖调节蛋白78(glucose regulated protein 78

GRP78)、C/EBP同源蛋白(C/EBP homologous protein，CHOP)的表达分布进行定性分析，RT-PCR及Western blot对髓核细胞中GRP78、CHOP进行mRNA和蛋白质水平的分析。

结果

透射电镜结果显示退变髓核细胞的内质网扩张、肿胀，正常片状折叠结构消失；免疫组化染色及Western blot检测结果均可见退变髓核组织GRP78、CHOP的表达升高；RT-PCR提示较之于正常组，退变组GRP78[(1.076±0.13)

(2.471±0.53)

]

、CHOP[(1.09±0.21)

(6.873±1.4)

]

明显升高(

0.05)。

结论

退变髓核细胞中内质网应激水平较正常髓核细胞升高，提示内质网应激可能在髓核细胞退变过程中发挥作用。

Abstract

Objective

To investigate the difference in the levels of endoplasmic reticulum (ER) stress between degenerative and normal human nucleus pulposus cells.

Methods

Nucleus pulposus tissues were collected from specimens of normal and degenerative intervertebral discs from 9 surgical patients (mean age 33 years) admitted in the Department of Orthopedic Surgery

Navy General Hospital between January

2016 and June

2017. The nucleus pulposus cells (NPCs) were isolated and cultured

and the morphology of the ER was observed using transmission electron microscopy (TEM). The expression levels of 2 ER stress-related molecules

namely glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP)

were analyzed using immunohistochemical assay

real-time PCR and Western blotting.

Results

TEM revealed obvious ER dilation and swelling in degenerative NPCs as compared with normal NPCs. Immunohistochemical assay and Western blotting showed obviously increased expressions of GRP78 and CHOP proteins in degenerative NPCs. GRP78 and CHOP mRNA expressions were also significantly increased in degenerative as compared with normal NPCs (2.471±0.53

1.076±0.13

and 6.873±1.4

1.09±0.21

respectively;

0.05).

Conclusion

The abnormal morphology of ER and increased expression of ER stress markers in degenerative NPCs suggest the involvement of ER stress in the development of NPC degeneration.

关键词

Keywords

references

WALTER P, RON D. The unfolded protein response: from stress pathway to homeostatic regulation[J]. Science, 2011, 334(6059): 1081-1086. DOI: 10.1126/science.1209038.

KEPLER C K, PONNAPPAN R K, TANNOURY C A, et al . The molecular basis of intervertebral disc degeneration[J ] . Spine J, 2013, 13(3): 318-330. DOI: 10.1016/j.spinee.2012.12.003.

WUERTZ K, VO N, KLETSAS D, et al . Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-kappaB and MAP kinases[J ] . Eur Cell Mater, 2012, 23: 103-119, 119-120.

KADOW T, SOWA G, VO N, et al . Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions?[J ] . Clin Orthop Relat Res, 2015, 473(6): 1903-1912. DOI: 10.1007/s11999-014-3774-8.

RISBUD M V, SHAPIRO I M. Role of cytokines in intervertebral disc degeneration: pain and disc content[J]. Nat Rev Rheumatol, 2014, 10(1): 44-56. DOI: 10.1038/nrrheum.2013.160.

ADOLPH T E, NIEDERREITER L, BLUMBERG R S, et al . Endoplasmic reticulum stress and inflammation[J ] . Dig Dis, 2012, 30(4): 341-346. DOI: 10.1159/000338121.

WANG M, KAUFMAN R J. Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J]. Nature, 2016, 529(7586): 326-335. DOI: 10.1038/nature17041.

LI Y H, TARDIF G, HUM D, et al . The unfolded protein response genes in human osteoarthritic chondrocytes: PERK emerges as a potential therapeutic target[J ] . Arthritis Res Ther, 2016, 18: 172. DOI: 10.1186/s13075-016-1070-6.

CAMERON T L, GRESSHOFF I L, BELL K M, 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 Cartilage, 2 015, 23(4): 661-670. DOI: 10.1016/j.joca.2015.01.001.

PFIRRMANN C W, METZDORF A, ZANETTI M, et al . Magnetic resonance classification of lumbar intervertebral disc degeneration[J ] . Spine (Phila Pa 1976), 2001, 26(17): 1873-1878.

GOLOB A L, WIPF J E. Low back pain[J]. Med Clin North Am, 2014, 98(3): 405-428. DOI: 10.1016/j.mcna.2014.01.003.

BODDU N J, THEUS S, LUO S, et al . Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?[J ] . Adipocyte, 2014, 3(1): 10-18. DOI: 10.4161/adip.26684.

WANG S, KAUFMAN R J. How does protein misfolding in the endoplasmic reticulum affect lipid metabolism in the liver?[J]. Curr Opin Lipidol, 2014, 25(2): 125-132. DOI: 10.1097/MOL.0000000000000056.

SHIMODAIRA Y, TAKAHASHI S, KINOUCHI Y, et al . Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1alpha (IRE1alpha) in human colon cancer cells[J ] . Biochem Biophys Res Commun, 2014, 445(2): 524-533. DOI: 10.1016/j.bbrc.2014.02.054.

LI H, ZHANG X Y, WU T J, et al . Endoplasmic reticulum stress regulates rat mandibular cartilage thinning under compressive mechanical stress[J ] . J Biol Chem, 2013, 288(25): 18172-18183. DOI: 10.1074/jbc.M112.407296.

YAMABE S, HIROSE J, UEHARA Y, et al . Intracellular accumulation of advanced glycation end products induces apoptosis via endoplasmic reticulum stress in chondrocytes[J ] . FEBS J, 2013, 280(7): 1617-1629. DOI: 10.1111/febs.12170.

TAKADA K, HIROSE J, SENBA K, et al . Enhanced apoptotic and reduced protective response in chondrocytes following endoplasmic reticulum stress in osteoarthritic cartilage[J ] . Int J Exp Pathol, 2011, 92(4): 232-242. DOI: 10.1111/j.1365-2613.2010.00758.x.

XU D, JIN H, WEN J, et al . Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration[J ] . Pharmacol Res, 2017, 117: 357-369. DOI: 10.1016/j.phrs.2017.01.005.

XIE Z Y, CHEN L, ZHANG C, et al . Acid-Sensing Ion Channel 1a Regulates Fate of Rat Nucleus Pulposus Cells in Acid Stimulus Through Endoplasmic Reticulum Stress[J ] . Biores Open Access, 2018, 7(1): 2-9. DOI: 10.1089/biores.2017.0049.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Dynamic expression and significance of PACS-2 in non-alcoholic fatty liver disease

Role of endoplasmic reticulum stress in hypoxia/reoxygenation-induced inflammation in rat renal tubular epithelial cells

培养神经细胞透射电镜样本制备方法的探讨

大鼠膀胱平滑肌过度充盈后钙离子分布的变化

烟雾吸入性急性呼吸衰竭(ARF)发生机制的实验研究

Related Author

陈东风

王军

魏艳玲

王斌

陈潇迪

李砚

冯吉

熊吉

Related Institution

No data

⁰