Skip to main content
SpringerLink
Log in

Suppression of matrix degradation and amelioration of disc degeneration by a 970-nm diode laser via inhibition of the p38 MAPK pathway in a rabbit model

  • Original Article
  • Published:
Lasers in Medical Science Aims and scope Submit manuscript

Abstract

Intervertebral disc degeneration (IVDD) mainly manifests as an imbalance between the synthesis and degradation of cellular and extracellular matrix (ECM) components. The cytokine interleukin (IL)-1β-induced inflammatory response of intervertebral discs causes ECM degradation. The aim of this study was to investigate the effects of a 970-nm diode laser therapy (DLT) on inflammatory cytokine IL-1β and ECM degradation proteinases in nucleus pulposus (NP) tissues in a puncture-induced rabbit IVDD model. Thirty-six New Zealand white rabbits were randomly divided into six groups: the normal group, IVDD group, laser group, sham laser group, IVDD + anisomycin (p38MAPK signaling pathway agonist), and laser + anisomycin group. Effects of laser on IVDD progression were detected using radiographic and magnetic resonance imaging. Hematoxylin and eosin, Alcian blue, safranin O-fast green staining, western blotting, and immunohistochemistry staining were performed for the histological analysis and molecular mechanism underlying protection against puncture-induced matrix degradation in NP tissues by DLT. DLT reduced the degree of disc degeneration in the gross anatomy of the disc and increased the T2-weighted signal intensity of NP. Inflammatory cytokine IL-1β levels in the disc were significantly reduced after DLT suppressed the matrix-degrading proteinases MMP13 and ADAMTS-5 and upregulated the protein expression of collagen II and aggrecan. Moreover, it inhibited the p38MAPK signaling pathway in NP tissues in a puncture-induced rabbit IVDD model. DLT reduced puncture-induced overexpression of inflammatory cytokines, mainly IL-1β, thus inhibiting matrix degeneration of NP tissues and ameliorating IVDD. This may be related to inhibition of the p38 MAPK signaling pathway.

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

Similar content being viewed by others

Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

References

  1. Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira ML, Genevay S, Hoy D, Karppinen J, Pransky G, Sieper J, Smeets RJ, Underwood M, Lancet Low back pain series working group (2018) what low back pain is and why we need to pay attention. Lancet 391(10137):2356–2367. https://doi.org/10.1016/S0140-6736(18)30480-X

    Article  PubMed  Google Scholar 

  2. Roh EJ, Darai A, Kyung JW, Choi H, Kwon SY, Bhujel B, Kim KT, Han I (2021) Genetic therapy for intervertebral disc degeneration. Int J Mol Sci 22(4):1579. https://doi.org/10.3390/ijms22041579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schizas C, Kulik G, Kosmopoulos V (2010) Disc degeneration: current surgical options. Eur Cells Mater 20:306–315

    Article  CAS  Google Scholar 

  4. Dowdell J, Erwin M, Choma T, Vaccaro A, Iatridis J, Cho SK (2017) Intervertebral disk degeneration and repair. Neurosurgery 80(3S):S46–S54. https://doi.org/10.1093/neuros/nyw078

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sakai D, Grad S (2015) Advancing the cellular and molecular therapy for intervertebral disc disease. Adv Drug Deliv Rev 84:159–171. https://doi.org/10.1016/j.addr.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  6. Vo NV, Hartman RA, Patil PR, Risbud MV, Kletsas D, Iatridis JC, Hoyland JA, Le Maitre CL, Sowa GA, Kang JD (2016) Molecular mechanisms of biological aging in intervertebral discs. J Orthopaedic Res 34(8):1289–1306. https://doi.org/10.1002/jor.23195

    Article  Google Scholar 

  7. Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31(18):2151–2161. https://doi.org/10.1097/01.brs.0000231761.73859.2c

    Article  PubMed  Google Scholar 

  8. Liu W, Jin S, Huang M, Li Y, Wang Z, Wang P, Zhao X, Xia P, Feng J (2020) Duhuo jisheng decoction suppresses matrix degradation and apoptosis in human nucleus pulposus cells and ameliorates disc degeneration in a rat model. J Ethnopharmacol 250:112494. https://doi.org/10.1016/j.jep.2019.112494

    Article  CAS  PubMed  Google Scholar 

  9. Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG (2002) Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine 27(23):2631–2644. https://doi.org/10.1097/00007632-200212010-00002

    Article  PubMed  Google Scholar 

  10. Risbud MV, Shapiro IM (2014) Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol 10(1):44–56. https://doi.org/10.1038/nrrheum.2013.160

    Article  CAS  PubMed  Google Scholar 

  11. Navone SE, Marfia G, Giannoni A, Beretta M, Guarnaccia L, Gualtierotti R, Nicoli D, Rampini P, Campanella R (2017) Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration. Histol Histopathol 32(6):523–542. https://doi.org/10.14670/HH-11-846

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S (2020) The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother 131:110660. https://doi.org/10.1016/j.biopha.2020.110660

    Article  CAS  PubMed  Google Scholar 

  13. Studer RK, Aboka AM, Gilbertson LG, Georgescu H, Sowa G, Vo N, Kang JD (2007) p38 MAPK inhibition in nucleus pulposus cells: a potential target for treating intervertebral disc degeneration. Spine 32(25):2827–2833. https://doi.org/10.1097/BRS.0b013e31815b757a

    Article  PubMed  Google Scholar 

  14. Studer RK, Gilbertson LG, Georgescu H, Sowa G, Vo N, Kang JD (2008) p38 MAPK inhibition modulates rabbit nucleus pulposus cell response to IL-1. J Orthopaedic Res 26(7):991–998. https://doi.org/10.1002/jor.20604

    Article  CAS  Google Scholar 

  15. Wu PH, Kim HS, Jang IT (2020) Intervertebral disc diseases part 2: a review of the current diagnostic and treatment strategies for intervertebral disc disease. Int J Mol Sci 21(6):2135. https://doi.org/10.3390/ijms21062135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brouwer PA, Brand R, van den Akker-van Marle ME, Jacobs WC, Schenk B, van den Berg-Huijsmans AA, Koes BW, van Buchem MA, Arts MP, Peul WC (2015) Percutaneous laser disc decompression versus conventional microdiscectomy in sciatica: a randomized controlled trial. Spine J 15(5):857–865. https://doi.org/10.1016/j.spinee.2015.01.020

    Article  PubMed  Google Scholar 

  17. Ren L, Han Z, Zhang J, Zhang T, Yin J, Liang X, Guo H, Zeng Y (2014) Efficacy of percutaneous laser disc decompression on lumbar spinal stenosis. Lasers Med Sci 29(3):921–923. https://doi.org/10.1007/s10103-013-1429-8

    Article  PubMed  Google Scholar 

  18. Hellinger J (2004) Complications of non-endoscopic percutaneous laser disc decompression and nucleotomy with the neodymium: YAG laser 1064 nm. Photomed Laser Surg 22(5):418–422. https://doi.org/10.1089/pho.2004.22.418

    Article  CAS  PubMed  Google Scholar 

  19. Fusellier M, Colombier P, Lesoeur J, Youl S, Madec S, Gauthier O, Hamel O, Guicheux J, Clouet J (2016) Longitudinal comparison of enzyme- and laser-treated intervertebral disc by MRI, X-Ray, and histological analyses reveals discrepancies in the progression of disc degeneration: a rabbit study. Biomed Res Int 2016:5498271. https://doi.org/10.1155/2016/5498271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huang M, Dong W, Sun Y, He B (2021) Two dimensional automatic active shape model of degenerative disc repaired by low-intensity laser. Math Biosci Eng 18(4):4358–4371. https://doi.org/10.3934/mbe.2021219

    Article  PubMed  Google Scholar 

  21. Ashinsky BG, Gullbrand SE, Bonnevie ED, Mandalapu SA, Wang C, Elliott DM, Han L, Mauck RL, Smith HE (2019) Multiscale and multimodal structure-function analysis of intervertebral disc degeneration in a rabbit model. Osteoarthr Cartil 27(12):1860–1869. https://doi.org/10.1016/j.joca.2019.07.016

    Article  CAS  Google Scholar 

  22. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26(17):1873–1878. https://doi.org/10.1097/00007632-200109010-00011

    Article  CAS  PubMed  Google Scholar 

  23. Masuda K, Aota Y, Muehleman C, Imai Y, Okuma M, Thonar EJ, Andersson GB, An HS (2005) A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 30(1):5–14. https://doi.org/10.1097/01.brs.0000148152.04401.20

    Article  PubMed  Google Scholar 

  24. Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27(3):335–345. https://doi.org/10.1016/j.biomaterials.2005.06.038

    Article  CAS  PubMed  Google Scholar 

  25. Xia C, Zeng Z, Fang B, Tao M, Gu C, Zheng L, Wang Y, Shi Y, Fang C, Mei S, Chen Q, Zhao J, Lin X, Fan S, Jin Y, Chen P (2019) Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects. Free Radical Biol Med 143:1–15. https://doi.org/10.1016/j.freeradbiomed.2019.07.026

    Article  CAS  Google Scholar 

  26. Chen F, Jiang G, Liu H, Li Z, Pei Y, Wang H, Pan H, Cui H, Long J, Wang J, Zheng Z (2020) Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop. Bone Res 8:10. https://doi.org/10.1038/s41413-020-0087-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tian Y, Yuan W, Fujita N, Wang J, Wang H, Shapiro IM, Risbud MV (2013) Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB. Am J Pathol 182(6):2310–2321. https://doi.org/10.1016/j.ajpath.2013.02.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang WJ, Yu XH, Wang C, Yang W, He WS, Zhang SJ, Yan YG, Zhang J (2015) MMPs and ADAMTSs in intervertebral disc degeneration. Clinica Chimica Acta 448:238–246. https://doi.org/10.1016/j.cca.2015.06.023

    Article  CAS  Google Scholar 

  29. Zhou Y, Chen Z, Yang X, Cao X, Liang Z, Ma H, Zhao J (2021) Morin attenuates pyroptosis of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of the TXNIP/NLRP3/Caspase-1/IL-1β signaling pathway. Biochem Biophys Res Commun 559:106–112. https://doi.org/10.1016/j.bbrc.2021.04.090

    Article  CAS  PubMed  Google Scholar 

  30. Liu ZM, Lu CC, Shen PC, Chou SH, Shih CL, Chen JC, Tien YC (2021) Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway. Bone Joint Res 10(8):498–513. https://doi.org/10.1302/2046-3758.108.BJR-2020-0041.R3

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lei M, Zhao K, Hua W, Wang K, Li S, Wu X, Yang C (2021) An in vivo study of the effect of c-Jun on intervertebral disc degeneration in rats. Bioengineered 12(1):4320–4330. https://doi.org/10.1080/21655979.2021.1946459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Schindl A, Schindl M, Pernerstorfer-Schön H, Schindl L (2000) Low-intensity laser therapy: a review. J Invest Med 48(5):312–326

    CAS  Google Scholar 

  33. Borshchenko I, Sobol E, Shekhter A, Baskov A, Grin A, Borshchenko M (2022) Biological non-ablative repair of lumbar discs by transforaminal intradiscal laser irradiation: MRI quantitative analysis of the effects-preliminary report. Lasers Med Sci 37(1):155–162. https://doi.org/10.1007/s10103-020-03191-z

    Article  PubMed  Google Scholar 

  34. Sato M, Ishihara M, Kikuchi M, Mochida J (2011) The influence of Ho:YAG laser irradiation on intervertebral disc cells. Lasers Surg Med 43(9):921–926. https://doi.org/10.1002/lsm.21120

    Article  PubMed  Google Scholar 

  35. Hwang MH, Shin JH, Kim KS, Yoo CM, Jo GE, Kim JH, Choi H (2015) Low level light therapy modulates inflammatory mediators secreted by human annulus fibrosus cells during intervertebral disc degeneration in vitro. Photochem Photobiol 91(2):403–410. https://doi.org/10.1111/php.12415

    Article  CAS  PubMed  Google Scholar 

  36. Lemos GA, Rissi R, de Souza Pires IL, de Oliveira LP, de Aro AA, Pimentel ER, Palomari ET (2016) Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint. Lasers Med Sci 31(6):1051–1059. https://doi.org/10.1007/s10103-016-1946-3

    Article  PubMed  Google Scholar 

  37. Yamada EF, Bobinski F, Martins DF, Palandi J, Folmer V, da Silva MD (2020) Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats. J Biophotonics 13(1):e201900204. https://doi.org/10.1002/jbio.201900204

    Article  CAS  PubMed  Google Scholar 

  38. Streitparth F, Hartwig T, Walter T, De Bucourt M, Putzier M, Strube P, Bretschneider T, Freyhardt P, Maurer M, Renz D, Gebauer B, Hamm B, Teichgräber UK (2013) MR guidance and thermometry of percutaneous laser disc decompression in open MRI: an initial clinical investigation. Eur Radiol 23(10):2739–2746. https://doi.org/10.1007/s00330-013-2872-4

    Article  PubMed  Google Scholar 

  39. Ren L, Guo H, Zhang T, Han Z, Zhang L, Zeng Y (2013) Efficacy evaluation of percutaneous laser disc decompression in the treatment of lumbar disc herniation. Photomed Laser Surg 31(4):174–178. https://doi.org/10.1089/pho.2012.3402

    Article  PubMed  Google Scholar 

  40. Krupkova O, Sekiguchi M, Klasen J, Hausmann O, Konno S, Ferguson SJ, Wuertz-Kozak K (2014) Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats. Eur Cells Mater 28:372–386. https://doi.org/10.22203/ecm.v028a26

    Article  CAS  Google Scholar 

  41. Lee JH, Chiang MH, Chen PH, Ho ML, Lee HE, Wang YH (2018) Anti-inflammatory effects of low-level laser therapy on human periodontal ligament cells: in vitro study. Lasers Med Sci 33(3):469–477. https://doi.org/10.1007/s10103-017-2376-6

    Article  PubMed  Google Scholar 

  42. Shingyochi Y, Kanazawa S, Tajima S, Tanaka R, Mizuno H, Tobita M (2017) A low-level carbon dioxide laser promotes fibroblast proliferation and migration through activation of Akt, ERK, and JNK. Plos One 12(1):e0168937. https://doi.org/10.1371/journal.pone.0168937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Chen CH, Hung HS, Hsu SH (2008) Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway. Lasers Surg Med 40(1):46–54. https://doi.org/10.1002/lsm.20589

    Article  PubMed  Google Scholar 

  44. Ren X, Ge M, Qin X, Xu P, Zhu P, Dang Y, Gu J, Ye X (2016) S100a8/NF-κB signal pathway is involved in the 800-nm diode laser-induced skin collagen remodeling. Lasers Med Sci 31(4):673–678. https://doi.org/10.1007/s10103-016-1898-7

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Jingyue Zhang and Juan Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Pain Management, the Fourth Affiliated Hospital of Harbin Medical University, No.37, Yiyuan Street, Nangang District, Harbin, Heilongjiang Province, 150001, China

    Jingyue Zhang, Juan Sun, Dezhi Chen, Jiyu Kang, Chuan Peng, Xiaotao Chang & Huacheng Zhou

  2. Department of Pain Management, the First Affiliated Hospital of Harbin Medical University, No.25 Post Office Street, Nangang District, Harbin, Heilongjiang Province, 150001, China

    Jingyue Zhang

  3. NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, 150001, China

    Jingyue Zhang, Juan Sun, Dezhi Chen, Jiyu Kang, Chuan Peng, Xiaotao Chang & Huacheng Zhou

  4. Department of Anesthesiology, Chongqing Public Health Medical Center, Chongqing, 400036, China

    Juan Sun

Authors
  1. Jingyue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dezhi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiyu Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chuan Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaotao Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Huacheng Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Huacheng Zhou contributed to the study conception and design. Jingyue Zhang and Juan Sun conducted the main experiments, analyzed the data, and prepared the manuscript. Jingyue Zhang, Dezhi Chen, Jiyu Kang, Chuan Peng, and Xiaotao Chang performed the experiments. All the authors reviewed the manuscript.

Corresponding author

Correspondence to Huacheng Zhou.

Ethics declarations

Ethics approval

All animal experiments were approved by the Animal Ethics Committee of the Fourth Affiliated Hospital of Harbin Medical University.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Sun, J., Chen, D. et al. Suppression of matrix degradation and amelioration of disc degeneration by a 970-nm diode laser via inhibition of the p38 MAPK pathway in a rabbit model. Lasers Med Sci 38, 58 (2023). https://doi.org/10.1007/s10103-023-03717-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10103-023-03717-1

Keywords

Search

Navigation