Skip to main content

Advertisement

SpringerLink
Log in

RPL38 knockdown inhibits the inflammation and apoptosis in chondrocytes through regulating METTL3-mediated SOCS2 m6A modification in osteoarthritis

  • Original Research Article
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Background

Ribosomal protein L38 (RPL38) was found upregulated in osteoarthritic peripheral blood mononuclear cells, however, its role in progression of osteoarthritis has not been characterized.

Methods

The protein levels of RPL38 and SOCS2 in cartilage tissues from OA patients and controls were detected with Western blotting. IL-1β was used to stimulate primary chondrocytes to establish an OA cell model, and RPL38 siRNA (si-RPL38) was transfected into chondrocytes to investigate the effect of RPL38 knockdown on cell viability, apoptosis, inflammatory factor secretion and extracellular matrix degradation. Then, the mechanism that RPL38 regulate the SOCS2 expression and SOCS2-induced chondrocyte dysfunction was explored. The methyltransferase-like 3 (METTL3)-mediated m6A modification of SOCS2 mRNA was confirmed, and the interaction of RPL38 and METTL3 was verified. Moreover, the effects of SOCS2 overexpression on IL-1β-induced chondrocyte dysfunction and SOCS2 knockdown on the restoration of chondrocyte function by siRPL38 were investigated. Finally, RPL38 was knocked down in vivo and its role in OA progression was validated.

Results

RPL38 was upregulated and SOCS2 was downregulated in OA cartilages. RPL38 knockdown or SOCS2 overexpression either attenuated IL-1β-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation. RPL38 directly interacted with METTL3 and it inhibited SOCS2 expression through METTL3-mediated m6A modification. SOCS2 knockdown activated the JAK2/STAT3 proinflammatory pathway and reversed the effects of RPL38 knockdown on IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation. RPL38 knockdown alleviated cartilage tissue damage and ECM degradation in OA mice.

Conclusion

RPL38 knockdown inhibited osteoarthritic chondrocyte dysfunction and alleviated OA progression through promoting METTL3-m6A-mediated SOCS2 expression.

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

Similar content being viewed by others

Availability of materials

The datasets used during the present study are available from the corresponding author upon reasonable request.

References

  1. Nelson AE. Osteoarthritis year in review 2017: clinical. Osteoarthr Cartil. 2018;26(3):319–25.

    Article  CAS  Google Scholar 

  2. Singh P, Marcu KB, Goldring MB, et al. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann NY Acad Sci. 2019;1442(1):17–34.

    Article  CAS  Google Scholar 

  3. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019;393(10182):1745–59.

    Article  CAS  Google Scholar 

  4. Li B, Guan G, Mei L, et al. Pathological mechanism of chondrocytes and the surrounding environment during osteoarthritis of temporomandibular joint. J Cell Mol Med. 2021;25(11):4902–11.

    Article  Google Scholar 

  5. Shahid M, Manchi G, Slunsky P, et al. A systemic review of existing serological possibilities to diagnose canine osteoarthritis with a particular focus on extracellular matrix proteoglycans and protein. Pol J Vet Sci. 2017;20(1):189–201.

    Article  CAS  Google Scholar 

  6. Hoshi H, Akagi R, Yamaguchi S, et al. Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice. Cell Tissue Res. 2017;368(2):379–87.

    Article  CAS  Google Scholar 

  7. Sahin F, Qiu W, Wilentz RE, et al. RPL38, FOSL1, and UPP1 are predominantly expressed in the pancreatic ductal epithelium. Pancreas. 2005;30(2):158–67.

    Article  CAS  Google Scholar 

  8. Zheng B, Peng J, Mollayup A, et al. Construction of a prognostic prediction system for pancreatic ductal adenocarcinoma to investigate the key prognostic genes. Mol Med Rep. 2018;17(1):216–24.

    CAS  PubMed  Google Scholar 

  9. Ji H, Zhang X. RPL38 regulates the proliferation and apoptosis of gastric cancer via miR-374b-5p/VEGF signal pathway. Onco Targets Ther. 2020;13:6131–41.

    Article  Google Scholar 

  10. Shi T, Shen X, Gao G. Gene expression profiles of peripheral blood monocytes in osteoarthritis and analysis of differentially expressed genes. Biomed Res Int. 2019;2019:4291689.

    PubMed  PubMed Central  Google Scholar 

  11. Rico-Bautista E, Flores-Morales A, Fernández-Pérez L. Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. Cytokine Growth Factor Rev. 2006;17(6):431–9.

    Article  CAS  Google Scholar 

  12. Val CH, de Oliveira MC, Lacerda DR, et al. SOCS2 modulates adipose tissue inflammation and expansion in mice. J Nutr Biochem. 2020;76: 108304.

    Article  CAS  Google Scholar 

  13. Toscano ECB, Sousa L, Lima GK, et al. Neuroinflammation is associated with reduced SOCS2 and SOCS3 expression during intracranial HSV-1 infection. Neurosci Lett. 2020;736: 135295.

    Article  CAS  Google Scholar 

  14. de Andrés MC, Imagawa K, Hashimoto K, et al. Suppressors of cytokine signalling (SOCS) are reduced in osteoarthritis. Biochem Biophys Res Commun. 2011;407(1):54–9.

    Article  Google Scholar 

  15. Wang BW, Jiang Y, Yao ZL, et al. Aucubin protects chondrocytes against IL-1β-induced apoptosis in vitro and inhibits osteoarthritis in mice model. Drug Des Dev Ther. 2019;13:3529–38.

    Article  CAS  Google Scholar 

  16. Wang X, Fan J, Ding X, et al. Tanshinone I inhibits IL-1β-induced apoptosis, inflammation and extracellular matrix degradation in chondrocytes CHON-001 cells and attenuates murine osteoarthritis. Drug Des Dev Ther. 2019;13:3559–68.

    Article  CAS  Google Scholar 

  17. Xu J, Chen Q, Tian K, et al. m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncol Rep. 2020;44(3):973–86.

    Article  CAS  Google Scholar 

  18. Malemud CJ. Negative regulators of JAK/STAT signaling in rheumatoid arthritis and osteoarthritis. Int J Mol Sci. 2017;18(3):484.

    Article  Google Scholar 

  19. Hada S, Kaneko H, Sadatsuki R, et al. The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study. Osteoarthr Cartil. 2014;22(10):1583–9.

    Article  CAS  Google Scholar 

  20. Zhang J, Cheng F, Rong G, et al. Circular RNA hsa_circ_0005567 overexpression promotes M2 type macrophage polarization through miR-492/SOCS2 axis to inhibit osteoarthritis progression. Bioengineered. 2021;12(1):8920–30.

    Article  CAS  Google Scholar 

  21. Chen M, Wei L, Law CT, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2018;67(6):2254–70.

    Article  CAS  Google Scholar 

  22. Lim H, Kim HP. Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Arch Pharm Res. 2011;34(1):109–17.

    Article  CAS  Google Scholar 

  23. Letellier E, Haan S. SOCS2: physiological and pathological functions. Front Biosci (Elite Ed). 2016;8:189–204.

    Article  Google Scholar 

  24. Bao NN, Kong DY, Zhu D, et al. Influence of overexpression of SOCS2 on cells of DN rat. Asian Pac J Trop Med. 2015;8(7):583–9.

    Article  CAS  Google Scholar 

Download references

Funding

No applicable.

Author information

Authors and Affiliations

  1. Department of Orthopedics, Shaanxi Provincial People’s Hospital, Xi’an, 710065, Shaanxi, China

    Liang Shi, Le Ji & Shizhang Liu

  2. Department of Orthopedics, Weinan Central Hospital, Shengli Street, Linwei District, Weinan, 714000, Shaanxi, China

    Hongbo Hu, Pengxiao Sun, Zheng Li & Jianxin Zhang

Authors
  1. Liang Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongbo Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pengxiao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Le Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shizhang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jianxin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HH designed the experiments. LS, HH, PS, ZL and LJ performed the experimental work. SL and JZ performed statistical analysis and prepared the figures for the manuscript. HH wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hongbo Hu.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This study was approved by the Ethnic Committee of Shaanxi Provincial People's Hospital, and all patients had read and signed the informed consent. All animal care and experimental procedures were approved by the Ethics Committee of Shaanxi Provincial People's Hospital (SXSPPH-2020-022).

Additional information

Responsible Editor: Jason J. McDougall.

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

Shi, L., Hu, H., Sun, P. et al. RPL38 knockdown inhibits the inflammation and apoptosis in chondrocytes through regulating METTL3-mediated SOCS2 m6A modification in osteoarthritis. Inflamm. Res. 71, 977–989 (2022). https://doi.org/10.1007/s00011-022-01579-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-022-01579-x

Keywords

Search

Navigation