Skip to main content
SpringerLink
Log in

17β-Estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13

  • Original Paper
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

In our previous study, 17β-estradiol was proved to protect rat annulus fibrosus cells against apoptosis induced by interleukin-1β (IL-1β). However, whether 17β-estradiol has protective effect on rat nucleus pulposus cells remains unclear. The purpose of this study was to further explore the effects of 17β-estradiol on rat nucleus pulposus cells based on IL-1β-induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to detect apoptosis and revealed that IL-1β induced notable apoptosis, which was reversed by 17β-estradiol. Meanwhile, cell viability and binding ability were decreased by IL-1β, but activated caspase-3 was increased. However, all of the detected effects of IL-1β were eliminated by 17β-estradiol. Furthermore, real-time quantitative RT-PCR was used to further find that IL-1β downregulated expression level of type II collagen, aggrecan, tissue inhibitor of matrix metalloproteinase (TIMP)-1, while upregulated matrix metalloproteinase (MMP)-3, MMP-13 and Bcl-2, which was further confirmed by western blot. Finally, 17β-estradiol was proved to abolish the above negative effects of IL-1β. In summary, this work presented that IL-1β maybe induced apoptosis of rat nucleus pulposus cells, which was resisted by 17β-estradiol by down-regulating MMP-3 and MMP-13 via a mitochondrial pathway. This research provides a novel insight into the anti-apoptotic effect of 17β-estradiol on IL-1β-induced cytotoxicity, and may potentially lead to a better understanding of the clinical effects of 17β-estradiol, especially in terms of intervertebral disc degeneration.

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

Abbreviations

IVD:

Intervertebral disc

IVDD:

Intervertebral disc degeneration

ECM:

Extracellular matrix

NP:

Nucleus pulposus

NPCs:

Nucleus pulposus cells

IL-1β:

Interleukin-1β

E2,:

17β-estradiol

ICI:

ICI182780

TUNEL:

Terminal-deoxynucleoitidyl transferase mediated nick end labeling

RT-qPCR:

Reverse transcription and real-time quantitative polymerase chain reaction

MMP:

Matrix metalloproteinase

TIMP:

Tissue inhibitor of matrix metalloproteinase

FBS:

Fetal bovine serum

References

  1. Park JB, Kim KW, Han CW, Chang H (2001) Expression of Fas receptor on disc cells in herniated lumbar disc tissue. Spine 26:142–146

    Article  CAS  PubMed  Google Scholar 

  2. Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98:996–1003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine 20:1307–1314

    CAS  PubMed  Google Scholar 

  4. Zhou GQ, Yang F, Leung VYL (2008) Molecular and cellular biology of the intervertebral disc and the use of animal models. Current Orthop 22:267–273

    Article  Google Scholar 

  5. Le Maitre CL, Freemont AJ, Hoyland JA (2007) Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 9:R45

    Article  PubMed Central  PubMed  Google Scholar 

  6. Alini M, Roughley PJ, Antoniou J, Stoll T, Aebi M (2002) A biological approach to treating disc degeneration: not for today, but may be for tomorrow. Eur Spine J 11:S215–S220

    PubMed Central  PubMed  Google Scholar 

  7. Kroeber M, Unglaub F, Guehring T, Nerlich A, Hadi T, Lotz J, Carstens C (2005) Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model. Spine 30:181–187

    Article  PubMed  Google Scholar 

  8. Zhao CQ, Liu D, Li H, Jiang LS, Dai LY (2007) Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis. Apoptosis 12:2155–2161

    Article  CAS  PubMed  Google Scholar 

  9. Yang D, Wang D, Shimer A, Shen FH, Li X, Yang X (2014) Glutathione protects human nucleus pulposus cells from cell apoptosis and inhibition of matrix synthesis. Connect Tissue Res 55(2):132–139. doi:10.3109/03008207.2013.876421

    Article  CAS  PubMed  Google Scholar 

  10. Zhang CC, Cui GP, Hu JG, Xiao YZ, Zhou XS, Shao C, Lin Q, Zhou JS (2014) Effects of adenoviral vector expressing hIGF-1 on apoptosis in nucleus pulposus cells in vitro. Int J Mol Med 33(2):401–405. doi:10.3892/ijmm.2013.1586

    PubMed  Google Scholar 

  11. Park JB, Park IC, Park SJ, Jin HO, Lee JK, Riew KD (2006) Anti-apoptotic effects of caspase inhibitors on rat intervertebral disc cells. J Bone Joint Surg Am 88:771–779

    Article  PubMed  Google Scholar 

  12. Portt L, Norman G, Clapp C, Greenwood M (1813) Greenwood MT (2011) Anti-apoptosis and cell survival: a review. Biochim Biophys Acta 1:238–259. doi:10.1016/j.bbamcr.2010.10.010

    Google Scholar 

  13. Duprez L, Wirawan E, Vanden Berghe T, Vandenabeele P (2009) Major cell death pathways at a glance. Microbes Infect 11:1050–1062

    Article  CAS  PubMed  Google Scholar 

  14. Gupta S, Kass GE, Szegezdi E, Joseph B (2009) The mitochondrial death pathway: a promising therapeutic target in Diseases. J Cell Mol Med 13:1004–1033

    Article  CAS  PubMed  Google Scholar 

  15. Brunelle JK, Letai A (2009) Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 122:437–441

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M, Kroemer G (2010) Mitochondrial gateways to cancer. Mol Aspects Med 31:1–20

    Article  CAS  PubMed  Google Scholar 

  17. Mavrogonatou E, Angelopoulou MT, Kletsas D (2014) The catabolic effect of TNFα on bovine nucleus pulposus intervertebral disc cells and the restraining role of glucosamine sulfate in the TNFα-mediated up-regulation of MMP-3. J Orthop Res 32(12):1701–1707. doi:10.1002/jor.22725

    Article  CAS  PubMed  Google Scholar 

  18. Wang X, Wang H, Yang H, Li J, Cai Q, Shapiro IM, Risbud MV (2014) Tumor necrosis factor-α- and interleukin-1β-dependent matrix metalloproteinase-3 expression in nucleus pulposus cells requires cooperative signaling via syndecan 4 and mitogen-activated protein kinase-NF-κB axis: implications in inflammatory disc disease. Am J Pathol 184(9):2560–2572. doi:10.1016/j.ajpath.2014.06.006

    Article  CAS  PubMed  Google Scholar 

  19. Liu H, Pan H, Yang H, Wang J, Zhang K, Li X, Wang H, Ding W, Li B, Zheng Z (2014) LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression. J Orthop Res. doi: 10.1002/jor.22732. (in press)

  20. Gu SX, Li X, Hamilton JL, Chee A, Kc R, Chen D, An HS, Kim JS, Oh CD, Ma YZ, van Wijnen AJ, Im HJ (2014) MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc. Gene. doi: 10.1016/j.gene.2014.10.024. (in press)

  21. Knittel T, Mehde M, Kobold D, Saile B, Dinter C, Ramadori G (1999) Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and TGF-beta1. J Hepatol 30(1):48–60

    Article  CAS  PubMed  Google Scholar 

  22. Liu C, Wan X, Ye T, Fang F, Chen X, Chen Y, Dong Y (2014) Matrix Metalloproteinase 2 Contributes to Pancreatic Beta Cell Injury Induced by Oxidative Stress. PLoS One 9:e110227. doi:10.1371/journal.pone.0110227

    Article  PubMed Central  PubMed  Google Scholar 

  23. Wang L, Wu Y, Tan Y, Fei X, Deng Y, Cao H, Chen B, Wang H, Magdalou J, Chen L (2014) Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells. J Appl Toxicol 34(8):870–877. doi:10.1002/jat.2903

    Article  PubMed  Google Scholar 

  24. Yurube T, Takada T, Suzuki T, Kakutani K, Maeno K, Doita M, Kurosaka M, Nishida K (2012) Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration. Arthritis Res Ther 14:R51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Wang H, Ding W, Yang D, Gu T, Yang S, Bai Z (2014) Different concentrations of 17β-estradiol modulates apoptosis induced by interleukin-1β in rat annulus fibrosus cells. Mol Med Rep 10(5):2745–2751. doi:10.3892/mmr.2014.2514

    CAS  PubMed  Google Scholar 

  26. Yang SD, Ma L, Gu TX, Ding WY, Zhang F, Shen Y, Zhang YZ, Yang DL, Zhang D, Sun YP, Song YL (2014) 17β-Estradiol protects against apoptosis induced by levofloxacin in rat nucleus pulposus cells by upregulating integrin α2β1. Apoptosis 19(5):789–800. doi:10.1007/s10495-014-0965-4

    Article  CAS  PubMed  Google Scholar 

  27. Yang SD, Bai ZL, Zhang F, Ma L, Yang DL, Ding WY (2014) Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway. Toxicol Mech Methods 24(9):688–696. doi:10.3109/15376516.2014.963772

    Article  CAS  PubMed  Google Scholar 

  28. D’Amelio M, Tino E, Cecconi F (2008) The apoptosome: emerging insights and new potential targets for drug design. Pharm Res 25:740–751

    Article  PubMed Central  PubMed  Google Scholar 

  29. Zhong X, Rescorla FJ (2012) Cell surface adhesion molecules and adhesion-initiated signaling: understanding of anoikis resistance mechanisms and therapeutic opportunities. Cell Signal 24:393–401

    Article  CAS  PubMed  Google Scholar 

  30. Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME (2013) Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinol Metab 98(4):1376–1387. doi:10.1210/jc.2012-3780

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Lee JS, Ettinger B, Stanczyk FZ, Vittinghoff E, Hanes V, Cauley JA, Chandler W, Settlage J, Beattie MS, Folkerd E, Dowsett M, Grady D, Cummings SR (2006) Comparison of methods to measure low serum estradiol levels in postmenopausal women. J Clin Endocrinol Metab 91:3791–3797

    Article  CAS  PubMed  Google Scholar 

  32. Rothman MS, Carlson NE, Xu M, Wang C, Swerdloff R, Lee P, Goh VH, Ridgway EC, Wierman ME (2011) Reexamination of testosterone, dihydrotestosterone, estradiol and estrone levels across the menstrual cycle and in postmenopausal women measured by liquid chromatography-tandem mass spectrometry. Steroids 76:177–182

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Natural Science Fund of Hebei Province (No. H2014206075).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051, China

    Si-Dong Yang, Da-Long Yang, Ya-Peng Sun, Lei Ma & Wen-Yuan Ding

  2. Department of Medical Device, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051, China

    Bao-Lin Wang

  3. Department of Orthopaedic Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, China

    Shi-Qing Feng

  4. Hebei Provincial Key Laboratory of Orthopaedic Biomechanics, 139 Ziqiang Road, Shijiazhuang, 050051, China

    Wen-Yuan Ding

Authors
  1. Si-Dong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Da-Long Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Peng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bao-Lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shi-Qing Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wen-Yuan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wen-Yuan Ding.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, SD., Yang, DL., Sun, YP. et al. 17β-Estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13. Apoptosis 20, 348–357 (2015). https://doi.org/10.1007/s10495-015-1086-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-015-1086-4

Keywords

Search

Navigation