Skip to main content

Advertisement

SpringerLink
Log in

LncRNA NEAT1 regulates chondrocyte proliferation and apoptosis via targeting miR-543/PLA2G4A axis

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Osteoarthritis (OA), which is characterized by articular cartilage degeneration, shows a gradually increasing incidence with age. This study explored the molecular mechanism underlying the proliferation and apoptosis of chondrocytes during OA progression. In this study, chondrocytes were isolated from human knee cartilages. The targeted relationship among nuclear enriched abundant transcript 1 (NEAT1), microRNA-543 (miR-543) and PLA2G4A was predicted on TargetScan V7.2 and starBase and validated by performing dual-luciferase reporter assay. High-expressed NEAT1 was detected in OA cartilage and chondrocytes. NEAT1 was negatively correlated with miR-543 and was low-expressed in OA cartilage and PLA2G4A was negatively correlated with miR-543 and was high-expressed in OA cartilage. In OA chondrocytes, the overexpressed NEAT1 inhibited the expressions of p-Akt1 and Bcl-2 and upregulated that of matrix metalloprotease (MMP)-3, MMP-9, MMP-13, interleukin (IL)-6 and IL-8, but such effects of overexpressed NEAT1 were reversed by miR-543 mimic. SiRNA-NEAT1 exerted an opposite effect to NEAT1 overexpression on OA chondrocytes, but this could be reversed by miR-543 inhibitor. The effect of PLA2G4A overexpression was the opposite to miR-543 mimic on OA chondrocytes. In conclusion, NEAT1 could sponge miR-543 to induce PLA2G4A expression, inhibit chondrocyte proliferation and promote apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Cheng C, Gao S, Lei G. Association of osteopontin with osteoarthritis. Rheumatol Int. 2014;34(12):1627–31. https://doi.org/10.1007/s00296-014-3036-9.

    Article  PubMed  Google Scholar 

  2. Laslett LL, Quinn SJ, Winzenberg TM, Sanderson K, Cicuttini F, Jones G. A prospective study of the impact of musculoskeletal pain and radiographic osteoarthritis on health related quality of life in community dwelling older people. BMC Musculoskelet Disord. 2012;13:168. https://doi.org/10.1186/1471-2474-13-168.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Poole AR. An introduction to the pathophysiology of osteoarthritis. Front Biosci. 1999;4:D662–D67070. https://doi.org/10.2741/poole.

    Article  CAS  PubMed  Google Scholar 

  4. Guilak F, Nims RJ, Dicks A, Wu C-L, Meulenbelt I. Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol. 2018;71–72:40–50. https://doi.org/10.1016/j.matbio.2018.05.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis. Instr Course Lect. 2005;54:465–80.

    PubMed  Google Scholar 

  6. de Lange-Brokaar BJE, Ioan-Facsinay A, van Osch GJVM, Zuurmond AM, Schoones J, Toes REM, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20(12):1484–99. https://doi.org/10.1016/j.joca.2012.08.027.

    Article  PubMed  Google Scholar 

  7. Hwang HS, Kim HA. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci. 2015;16(11):26035–54. https://doi.org/10.3390/ijms161125943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zou L, Liu J, Lu H. Influence of protein kinase RIPK4 expression on the apoptosis and proliferation of chondrocytes in osteoarthritis. Mol Med Rep. 2018;17(2):3078–84. https://doi.org/10.3892/mmr.2017.8209.

    Article  CAS  PubMed  Google Scholar 

  9. Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307. https://doi.org/10.1016/j.cell.2013.02.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu Y, Lin L, Zou R, Wen C, Wang Z, Lin F. MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis. Cell Cycle. 2018;17(21–22):2411–22. https://doi.org/10.1080/15384101.2018.1526603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1):7–21. https://doi.org/10.1038/nrg3606.

    Article  CAS  PubMed  Google Scholar 

  12. Tang LP, Ding JB, Liu ZH, Zhou GJ. LncRNA TUG1 promotes osteoarthritis-induced degradation of chondrocyte extracellular matrix via miR-195/MMP-13 axis. Eur Rev Med Pharmacol Sci. 2018;22(24):8574–81. https://doi.org/10.26355/eurrev_201812_16620.

    Article  PubMed  Google Scholar 

  13. Xiao Y, Bao Y, Tang L, Wang L. LncRNA MIR4435–2HG is downregulated in osteoarthritis and regulates chondrocyte cell proliferation and apoptosis. J Orthop Surg Res. 2019;14(1):247. https://doi.org/10.1186/s13018-019-1278-7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8. https://doi.org/10.1016/j.cell.2011.07.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang Q, Wang W, Zhang F, Deng Y, Long Z. NEAT1/miR-181c regulates osteopontin (OPN)-mediated synoviocyte proliferation in osteoarthritis. J Cell Biochem. 2017;118(11):3775–844. https://doi.org/10.1002/jcb.26025.

    Article  CAS  PubMed  Google Scholar 

  16. Altman R, Alarcón G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum. 1991;34(5):505–14. https://doi.org/10.1002/art.1780340502.

    Article  CAS  PubMed  Google Scholar 

  17. Goguet-Rubio P, Klug RL, Sharma DL, Srikanthan K, Puri N, Lakhani VH, et al. Existence of a strong correlation of biomarkers and miRNA in females with metabolic syndrome and obesity in a population of West Virginia. Int J Med Sci. 2017;14(6):543–53. https://doi.org/10.7150/ijms.18988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1890–6. https://doi.org/10.1016/j.joca.2015.02.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fathollahi A, Aslani S, Jamshidi A, Mahmoudi M. Epigenetics in osteoarthritis: novel spotlight. J Cell Physiol. 2019;234(8):12309–24. https://doi.org/10.1002/jcp.28020.

    Article  CAS  PubMed  Google Scholar 

  20. Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta. 2012;1824(1):133–45. https://doi.org/10.1016/j.bbapap.2011.06.020.

    Article  CAS  PubMed  Google Scholar 

  21. Kim HA, Blanco FJ. Cell death and apoptosis in osteoarthritic cartilage. Curr Drug Targets. 2007;8(2):333–45. https://doi.org/10.2174/138945007779940025.

    Article  CAS  PubMed  Google Scholar 

  22. Thomas CM, Fuller CJ, Whittles CE, Sharif M. Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthritis Cartilage. 2007;15(1):27–34. https://doi.org/10.1016/j.joca.2006.06.012.

    Article  CAS  PubMed  Google Scholar 

  23. Wang Z, Hao J, Chen D. Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) regulates proliferation, apoptosis, and inflammation of chondrocytes via the miR-181a/Glycerol-3-phosphate dehydrogenase 1-Like (GPD1L) Axis. Med Sci Monit. 2019;25:8084–94. https://doi.org/10.12659/MSM.918416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li J, Huang J, Dai L, Yu D, Chen Q, Zhang X, et al. miR-146a, an IL-1β responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4. Arthritis Res Ther. 2012;14(2):75. https://doi.org/10.1186/ar3798.

    Article  CAS  Google Scholar 

  25. Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, et al. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem Pharmacol. 2019;165:49–65. https://doi.org/10.1016/j.bcp.2019.02.036.

    Article  CAS  PubMed  Google Scholar 

  26. Liu F, Liu X, Yang Y, Sun Z, Deng S, Jiang Z, et al. NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis. Cell Biol Int. 2019. https://doi.org/10.1002/cbin.11291.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wu Y, Lu X, Shen B, Zeng Y. The therapeutic potential and role of miRNA, lncRNA, and circRNA in osteoarthritis. Curr Gene Ther. 2019;19(4):255–63. https://doi.org/10.2174/1566523219666190716092203.

    Article  CAS  PubMed  Google Scholar 

  28. Cao L, Wang Y, Wang Q, Huang J. LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting as a sponge of miR-206 to modulate CCND1 expression. Biomed Pharmacother. 2018;106:1220–6. https://doi.org/10.1016/j.biopha.2018.07.048.

    Article  CAS  PubMed  Google Scholar 

  29. Karaliotas GI, Mavridis K, Scorilas A, Babis GC. Quantitative analysis of the mRNA expression levels of BCL2 and BAX genes in human osteoarthritis and normal articular cartilage: An investigation into their differential expression. Mol Med Rep. 2015;12(3):4514–21. https://doi.org/10.3892/mmr.2015.3939.

    Article  CAS  PubMed  Google Scholar 

  30. He B, Tao H, Wei A, Liu S, Li X, Chen R. Protection of carboxymethylated chitosan on chondrocytes from nitric oxide-induced apoptosis by regulating phosphatidylinositol 3-kinase/Akt signaling pathway. Biochem Biophys Res Commun. 2016;479(2):380–6. https://doi.org/10.1016/j.bbrc.2016.09.084.

    Article  CAS  PubMed  Google Scholar 

  31. Hu P-F, Chen W-P, Bao J-P, Wu L-D. Paeoniflorin inhibits IL-1β-induced chondrocyte apoptosis by regulating the Bax/Bcl-2/caspase-3 signaling pathway. Mol Med Rep. 2018;17(4):6194–200. https://doi.org/10.3892/mmr.2018.8631.

    Article  CAS  PubMed  Google Scholar 

  32. Huang MC, Chen LY, Chang HM, Liang XY, Chen CK, Cheng WJ, et al. Decreased blood levels of oxytocin in ketamine-dependent patients during early abstinence. Front Psychiatry. 2018;9:633. https://doi.org/10.3389/fpsyt.2018.00633.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ko JH, Kang YM, Yang JH, Kim JS, Lee WJ, Kim SH, et al. Regulation of MMP and TIMP expression in synovial fibroblasts from knee osteoarthritis with flexion contracture using adenovirus-mediated relaxin gene therapy. Knee. 2019;26(2):317–29. https://doi.org/10.1016/j.knee.2019.01.010.

    Article  PubMed  Google Scholar 

  34. Fei J, Liang B, Jiang C, Ni H, Wang L. Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model. Biomed Pharmacother. 2019;109:1586–92. https://doi.org/10.1016/j.biopha.2018.09.161.

    Article  CAS  PubMed  Google Scholar 

  35. Chen Y, Lin Y, Bai Y, Cheng D, Bi Z. A Long Noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network identifies eight lncRNA biomarkers in patients with osteoarthritis of the knee. Med Sci Monit. 2019;25:2058–65. https://doi.org/10.12659/MSM.915555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu Z, Ren Z, Zhang J, Chuang CC, Kandaswamy E, Zhou T, et al. Role of ROS and nutritional antioxidants in human diseases. Front Physiol. 2018;9:477. https://doi.org/10.3389/fphys.2018.00477.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zhao H, Diao C, Wang X, Xie Y, Liu Y, Gao X, et al. MiR-543 promotes migration, invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting phospholipase A2 group IVA. Cell Physiol Biochem Internat J Exp Pharmacol. 2018;48(4):1595–604. https://doi.org/10.1159/000492281.

    Article  CAS  Google Scholar 

  38. Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11(2):136–40. https://doi.org/10.1038/ni.1831.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No.1, East Jianshe Road, Zhengzhou, 450000, Henan Province, China

    Peng Xiao, Xu Zhu, Jinpeng Sun, Yuhang Zhang, Weijian Qiu, Jianqiang Li & Xuejian Wu

Authors
  1. Peng Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinpeng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuhang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weijian Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianqiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuejian Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Substantial contributions to conception and design: PX, XZ. Data acquisition, data analysis and interpretation: JS, YZ, WQ, JL, XW. Drafting the article or critically revising it for important intellectual content: PX, XZ. Final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: All authors.

Corresponding author

Correspondence to Xuejian Wu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, P., Zhu, X., Sun, J. et al. LncRNA NEAT1 regulates chondrocyte proliferation and apoptosis via targeting miR-543/PLA2G4A axis. Human Cell 34, 60–75 (2021). https://doi.org/10.1007/s13577-020-00433-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-020-00433-8

Keywords

Search

Navigation