Issue

Vol. 66 No. 3: Issue 3

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Comprehensive multi-factors reveal the pathogenesis of degenerative intervertebral disc

https://doi.org/10.14715/cmb/2020.66.3.10
Kahaer Aikenmu
Department of Spine, TCM Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830000, China
Zhenbin Wang
Department of Spine, The Fourth Affiliated Hospital of Xinjiang Medical University Urumqi, Xinjiang 830000, China
Qingcai Meng
Department of Orthopedics, TCM Hospital of Xinjiang Uygur Autonomous Region, Xinjiang 830000, China

Corresponding Author(s) : Qingcai Meng

xiaoru@inbox.ru

Cellular and Molecular Biology, Vol. 66 No. 3: Issue 3

Abstract

Intervertebral Disc (IVD) is a moderately moving joint that provides load transfer and flexibility to the entire spine. Although healthy IVD can balance the turnover of slow-synthesis matrices, this balance is often disrupted that leading to the development of degenerative diseases. The pathogenesis and treatment mechanism of Intervertebral Disc Degeneration (IDD) has always been the focus of scientific research, but its pathogenesis is still unknown. Therefore, this study is based on a modular approach to in-depth analysis and explore the genes of IDD, intended to identify the molecular process of disc degeneration. Firstly, the data related to Intervertebral Disc Degeneration and normal intervertebral disc were downloaded from the GEO database. The differential analysis of two kinds of data was performed to obtain differential gene expression profiles. Secondly, mapping those differential genes to Cytoscape to construct protein-protein interaction networks (PPIs). Then, the module gene was subjected to enrichment analysis of GO function and KEGG pathway. Finally, non-coding RNAs (ncRNAs) and transcription factors that regulate the module are predicted based on hypergeometric testing. In summary, we identified 22 co-expression modules, and the enrichment analysis results revealed that the module genes were significantly involved in the regulation of definite biotic procedures. In conclusion, we recognized the ncRNA pivot (including miR-193b-3p, CRNDE, etc.) and TF pivot (including E2F1, E2F4, etc.) that significantly regulate dysfunction modules.

Keywords

Intervertebral disc degeneration Protein interaction network Enrichment Co-expression analysis Regulatory factors.
Aikenmu, K., Wang, Z., & Meng, Q. (2020). Comprehensive multi-factors reveal the pathogenesis of degenerative intervertebral disc. Cellular and Molecular Biology, 66(3), 65–71. https://doi.org/10.14715/cmb/2020.66.3.10
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Gonzalez Martinez E, Garcia-Cosamalon J, Cosamalon-Gan I, Esteban Blanco M, Garcia-Suarez O, Vega JA. Biology and mechanobiology of the intervertebral disc. Neurocirugia. 2017;28(3):135-40.
  2. Smith LJ, Nerurkar NL, Choi KS, Harfe BD, Elliott DM. Degeneration and regeneration of the intervertebral disc: lessons from development. Disease models & mechanisms. 2011;4(1):31-41.
  3. Li X, Dou Q, Kong Q. Repair and Regenerative Therapies of the Annulus Fibrosus of the Intervertebral Disc. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2016;26(2):138-44.
  4. Yee A, Lam MP, Tam V, Chan WC, Chu IK, Cheah KS, et al. Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis. Osteoarthritis and cartilage. 2016;24(3):503-13.
  5. Sharifi S, Bulstra SK, Grijpma DW, Kuijer R. Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus. Journal of tissue engineering and regenerative medicine. 2015;9(10):1120-32.
  6. Setton LA, Chen J. Cell mechanics and mechanobiology in the intervertebral disc. Spine. 2004;29(23):2710-23.
  7. Wan ZY, Sun Z, Song F, Chen YF, Zhang WL, Wang HQ, et al. Downregulated interleukin 37 expression associated with aggravation of intervertebral disc degeneration. International journal of clinical and experimental pathology. 2014;7(2):656-62.
  8. Hanaei S, Abdollahzade S, Sadr M, Mirbolouk MH, Khoshnevisan A, Rezaei N. Association of IL10 and TGFB single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population: a case control study. BMC medical genetics. 2018;19(1):59.
  9. Lin P, Fu Q. [Association of collagen type I alpha1 Sp1 polymorphism with intervertebral disc degeneration in Han elderly people]. Sichuan da xue xue bao Yi xue ban = Journal of Sichuan University Medical science edition. 2014;45(1):62-5.
  10. Dudek M, Yang N, Ruckshanthi JP, Williams J, Borysiewicz E, Wang P, et al. The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration. Annals of the rheumatic diseases. 2017;76(3):576-84.
  11. Huang Y, Jiang T, Chen J, Yin GY, Fan J. Effects of kartogenin on the attenuated nucleus pulposus cell degeneration of intervertebral discs induced by interleukin-1beta and tumor necrosis factor-alpha. International journal of molecular medicine. 2018;41(2):749-56.
  12. Wang YF, Levene HB, Gu W, Huang CC. Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices. Annals of biomedical engineering. 2017;45(9):2098-108.
  13. Xu TT, Liao F, Jin HT, Tong PJ, Xiao LW, Wu CL. [Research advance on intervertebral disc degeneration and cell death]. Zhongguo gu shang = China journal of orthopaedics and traumatology. 2015;28(7):673-8.
  14. Li X, Cui J, Sun G, Tan J, Li L. [RESEARCH PROGRESS OF microRNA IN INTERVERTEBRAL DISC DEGENERATION]. Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery. 2015;29(10):1312-6.
  15. Hu B, Xu C, Tian Y, Shi C, Zhang Y, Deng L, et al. Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration. Oncotarget. 2017;8(30):49303-17.
  16. Wu N, Chen J, Liu H, Zhao L, Liu S, Liu J, et al. The involvement of ADAMTS-5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2014;32(5):686-94.
  17. Li XC, Tang Y, Wu JH, Yang PS, Wang DL, Ruan DK. Characteristics and potentials of stem cells derived from human degenerated nucleus pulposus: potential for regeneration of the intervertebral disc. BMC musculoskeletal disorders. 2017;18(1):242.
  18. Sivan SS, Wachtel E, Roughley P. Structure, function, aging and turnover of aggrecan in the intervertebral disc. Biochimica et biophysica acta. 2014;1840(10):3181-9.
  19. Jin LZ, Lu JS, Gao JW. Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration. Bioscience reports. 2018;38(3).
  20. Meyer JN, Leuthner TC, Luz AL. Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology. 2017;391:42-53.
  21. Sakai D, Mochida J, Yamamoto Y, Toh E, Iwashina T, Miyazaki T, et al. Immortalization of human nucleus pulposus cells by a recombinant SV40 adenovirus vector: establishment of a novel cell line for the study of human nucleus pulposus cells. Spine. 2004;29(14):1515-23.
  22. Sun Z, Zhang M, Zhao XH, Liu ZH, Gao Y, Samartzis D, et al. Immune cascades in human intervertebral disc: the pros and cons. International journal of clinical and experimental pathology. 2013;6(6):1009-14.
  23. Ouyang ZH, Wang WJ, Yan YG, Wang B, Lv GH. The PI3K/Akt pathway: a critical player in intervertebral disc degeneration. Oncotarget. 2017;8(34):57870-81.
  24. Chen J, Jia YS, Liu GZ, Sun Q, Zhang F, Ma S, et al. Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/beta-catenin signaling pathway. Biochemical and biophysical research communications. 2017;491(3):668-74.
  25. Chen B, Liu Y, Zhang Y, Li J, Cheng K, Cheng L. IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-alpha Through the JAK-STAT Signaling Pathway. Inflammation. 2017;40(2):612-22.
  26. Suzuki S, Fujita N, Fujii T, Watanabe K, Yagi M, Tsuji T, et al. Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of Intervertebral Disc Degeneration. Spine. 2017;42(14):E817-E24.
  27. Wang J, Nisar M, Huang C, Pan X, Lin D, Zheng G, et al. Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration. Experimental & molecular medicine. 2018;50(11):146.
  28. Chang ZK, Meng FG, Zhang ZQ, Mao GP, Huang ZY, Liao WM, et al. MicroRNA-193b-3p regulates matrix metalloproteinase 19 expression in interleukin-1beta-induced human chondrocytes. Journal of cellular biochemistry. 2018;119(6):4775-82.
  29. Li Z, Tang Y, Xing W, Dong W, Wang Z. LncRNA, CRNDE promotes osteosarcoma cell proliferation, invasion and migration by regulating Notch1 signaling and epithelial-mesenchymal transition. Experimental and molecular pathology. 2018;104(1):19-25.
  30. Sun ZQ, Shi K, Zhou QB, Zeng XY, Liu J, Yang SX, et al. MiR-590-3p promotes proliferation and metastasis of colorectal cancer via Hippo pathway. Oncotarget. 2017;8(35):58061-71.
  31. Yu A, Bailey AD, Weiner AM. Metaphase fragility of the human RNU1 and RNU2 loci is induced by actinomycin D through a p53-dependent pathway. Human molecular genetics. 1998;7(4):609-17.
  32. Denechaud PD, Fajas L, Giralt A. E2F1, a Novel Regulator of Metabolism. Frontiers in endocrinology. 2017;8:311.
  33. Ji SC, Han N, Liu Y, Li G, Sun Z, Li Z. Identification of genes associated with disc degeneration using bioinformatics. Biotechnic & histochemistry : official publication of the Biological Stain Commission. 2015;90(5):353-60.
  34. Zenke K, Muroi M, Tanamoto KI. IRF1 supports DNA binding of STAT1 by promoting its phosphorylation. Immunology and cell biology. 2018;96(10):1095-103.
  35. Lu K, Li HY, Yang K, Wu JL, Cai XW, Zhou Y, et al. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem cell research & therapy. 2017;8(1):108.
  36. Gnanaprakasam JN, Wang R. MYC in Regulating Immunity: Metabolism and Beyond. Genes. 2017;8(3).
  37. Ruiz-Perez MV, Henley AB, Arsenian-Henriksson M. The MYCN Protein in Health and Disease. Genes. 2017;8(4).
  38. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic acids research. 2013;41(Database issue):D991-5.
  39. Yi, Y., et al., RAID v2.0: an updated resource of RNA-associated interactions across organisms. Nucleic Acids Res, 2017. 45(D1): p. D115-D118.
  40. Han, H., et al., TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res, 2018. 46(D1): p. D380-D386.
  41. Ritchie, ME, Phipson, B, Wu, D, Hu, Y, Law, CW, Shi, W, and Smyth, GK (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 43, e47. http://nar.oxfordjournals.org/content/43/7/e47
  42. Law, CW, Chen, Y, Shi, W, Smyth, GK (2014). Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biology 15, R29. http://genomebiology.com/2014/15/2/R29
  43. Smyth, GK. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004; 3: 1-26.
  44. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003. 13(11): 2498-504.
  45. Nepusz T, Yu H, Paccanaro A. Detecting overlapping protein complexes in protein-protein interaction networks. Nat Methods 2012; 9(5):471-2.
  46. Yu G, Wang LG, Han Y, He QY. Clusterprofiler: an R package for comparing biological themes among gene clusters. OMICS 2012. 16(5): p. 284-7.
  47. Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 2005; 21(16): 3448-9.
  48. Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosanol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
  49. Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: Association of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
  50. Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
  51. Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G: Non-parametric partial least squares–discriminant analysis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
  52. Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T and Lin Q: Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
  53. Lou Y, Yang J, Wang L, Chen X, Xin X and Liu Y: The clinical efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
  54. Nie Y, Luo F and Lin Q: Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
  55. Ren Y, Jiao X and Zhang L: Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
  56. Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
  57. Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryzanol modifies high fat diet-induced obesity, liver gene expression profile, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
  58. Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 829 Download : 445