Cell Biochemistry and Biophysics

, Volume 69, Issue 3, pp 439–444 | Cite as

Correlation of Matrix Metalloproteinases-1 and Tissue Inhibitor of Metalloproteinases-1 with Patient Age and Grade of Lumbar Disk Herniation

  • Haidong Xu
  • Qiang Mei
  • Jin He
  • Gang Liu
  • Jianning Zhao
  • Bin XuEmail author
Original Paper


The authors studied the nuclear magnetic resonance films and the expression of MMP-1 and TIMP-1 in disk specimens’ of patients who had undergone operations for lumbar disk herniation. Forty-one lumbar disk patients were evaluated imaging for degenerative changes and their disk specimens immunohistochemical expression of MMP-1 and TIMP-1. The degree of degenerative changes was based on magnetic resonance imaging films. Sections of disk immunostained for MMP-1 and TIMP-1 were evaluated semiquantitatively. Patients were categorized in three age groups: <30 years, from 30 to 60 years, and >60 years of age. The expressions of MMP-1 and TIMP-1 were related to patients’ age and degree of degenerative changes. There were statistical differences in the expression of MMP-1 and TIMP-1 between the age and degree of degenerative changes groups. With the degree of degenerative changes, the expression of MMP-1 and TIMP-1 increased obviously. But in old age group, the expression of MMP-1/TIMP-1 was higher than the young groups. The expressions of MMP-1 and TIMP-1 were strongly correlated to the age and the degree of the degenerative changes. An important finding in this study is the unbalance of the expression of MMP-1 and TIMP-1 along with the growth of the age.


MMP-1 TIMP-1 Lumbar spine herniation Immunohistochemistry 



Matrix metalloproteinases-1


Tissue inhibitor of metalloproteinases-1


Diaminobenzidine tetrahydrochloride


Conflict of interest

The authors have no conflict of interest to declare.


  1. 1.
    Rutges, J. P., Kummer, J. A., Oner, F. C., Verbout, A. J., Castelein, R. J., Roestenburg, H. J., et al. (2008). Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels. Journal of Pathology, 214(4), 523–530. doi: 10.1002/path.2317.PubMedCrossRefGoogle Scholar
  2. 2.
    Brisby, H. (2006). Pathology and possible mechanisms of nervous system response to disc degeneration. Journal of Bone and Joint Surgery American Volumes, 88(Suppl 2), 68–71.CrossRefGoogle Scholar
  3. 3.
    Albert, H. B., Briggs, A. M., Kent, P., Byrhagen, A., Hansen, C., & Kjaergaard, K. (2011). The prevalence of MRI-defined spinal pathoanatomies and their association with modic changes in individuals seeking care for low back pain. European Spine Journal, 20(8), 1355–1362. doi: 10.1007/s00586-011-1794-6.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Hancock, M. J., Koes, B., Ostelo, R., & Peul, W. (2011). Diagnostic accuracy of the clinical examination in identifying the level of herniation in patients with sciatica. Spine (Phila Pa 1976), 36(11), E712–E719. doi: 10.1097/BRS.0b013e3181ee7f78.CrossRefGoogle Scholar
  5. 5.
    Rutges, J. P., Nikkels, P. G., Oner, F. C., Ottink, K. D., Verbout, A. J., Castelein, R. J., et al. (2010). The presence of extracellular matrix degrading metalloproteinases during fetal development of the intervertebral disc. European Spine Journal, 19(8), 1340–1346. doi: 10.1007/s00586-010-1378-x.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Risbud, M. V., & Shapiro, I. M. (2013). Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nature Reviews Rheumatology,. doi: 10.1038/nrrheum.2013.160.PubMedGoogle Scholar
  7. 7.
    Wang, S. L., Yu, Y. L., Tang, C. L., & Lv, F. Z. (2013). Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration. Experimental and Therapeutic Medicine, 6(6), 1522–1526.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Zigouris, A., Batistatou, A., Alexiou, G. A., Pachatouridis, D., Mihos, E., Drosos, D., et al. (2011). Correlation of matrix metalloproteinases-1 and -3 with patient age and grade of lumbar disc herniation. Journal of Neurosurgery Spine, 14(2), 268–272. doi: 10.3171/2010.9.SPINE09935.PubMedCrossRefGoogle Scholar
  9. 9.
    Steffens, D., Hancock, M. J., Maher, C. G., Williams, C., Jensen, T. S., & Latimer, J. (2013). Does magnetic resonance imaging predict future low back pain? A systematic review. European Journal of Pain,. doi: 10.1002/j.1532-2149.2013.00427.x.PubMedGoogle Scholar
  10. 10.
    Tibiletti, M., Galbusera, F., Ciavarro, C., & Brayda-Bruno, M. (2013). Is the transport of a gadolinium-based contrast agent decreased in a degenerated or aged disc? A post contrast MRI study. PLoS One, 8(10), e76697. doi: 10.1371/journal.pone.0076697.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Ayturk, U. M., Gadomski, B., Schuldt, D., Patel, V., & Puttlitz, C. M. (2012). Modeling degenerative disk disease in the lumbar spine: A combined experimental, constitutive, and computational approach. Journal of Biomechanical Engineering, 134(10), 101003. doi: 10.1115/1.4007632.PubMedCrossRefGoogle Scholar
  12. 12.
    Hayes, A. J., Smith, S. M., Gibson, M. A., & Melrose, J. (2011). Comparative immunolocalization of the elastin fiber-associated proteins fibrillin-1, LTBP-2, and MAGP-1 with components of the collagenous and proteoglycan matrix of the fetal human intervertebral disc. Spine (Phila Pa 1976), 36(21), E1365–E1372. doi: 10.1097/BRS.0b013e31821fd23e.CrossRefGoogle Scholar
  13. 13.
    Ayturk, U. M., Garcia, J. J., & Puttlitz, C. M. (2010). The micromechanical role of the annulus fibrosus components under physiological loading of the lumbar spine. Journal of Biomechanical Engineering, 132(6), 061007. doi: 10.1115/1.4001032.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith, L. J., & Fazzalari, N. L. (2009). The elastic fibre network of the human lumbar anulus fibrosus: Architecture, mechanical function and potential role in the progression of intervertebral disc degeneration. European Spine Journal, 18(4), 439–448. doi: 10.1007/s00586-009-0918-8.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Goupille, P., Jayson, M. I., Valat, J. P., & Freemont, A. J. (1998). Matrix metalloproteinases: The clue to intervertebral disc degeneration? Spine (Phila Pa 1976), 23(14), 1612–1626.CrossRefGoogle Scholar
  16. 16.
    Bachmeier, B. E., Nerlich, A., Mittermaier, N., Weiler, C., Lumenta, C., Wuertz, K., et al. (2009). Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. European Spine Journal, 18(11), 1573–1586. doi: 10.1007/s00586-009-1031-8.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Belo, V. A., Souza-Costa, D. C., Luizon, M. R., Lanna, C. M., Carneiro, P. C., Izidoro-Toledo, T. C., et al. (2012). Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children. International Journal of Obesity (London), 36(1), 69–75. doi: 10.1038/ijo.2011.169.CrossRefGoogle Scholar
  18. 18.
    Wei, L., & Shi, Y. B. (2005). Matrix metalloproteinase stromelysin-3 in development and pathogenesis. Histology and Histopathology, 20(1), 177–185.PubMedGoogle Scholar
  19. 19.
    Murphy, G. (2011). Tissue inhibitors of metalloproteinases. Genome Biology, 12(11), 233. doi: 10.1186/gb-2011-12-11-233.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Bradley, L. M., Douglass, M. F., Chatterjee, D., Akira, S., & Baaten, B. J. (2012). Matrix metalloprotease 9 mediates neutrophil migration into the airways in response to influenza virus-induced toll-like receptor signaling. PLoS Pathogens, 8(4), e1002641. doi: 10.1371/journal.ppat.1002641.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Zhang, J., Yang, L., Tang, Z., Xue, R., Wang, Y., Luo, Z., et al. (2009). Expression of MMPs and TIMPs family in human ACL and MCL fibroblasts. Connective Tissue Research, 50(1), 7–13. doi: 10.1080/03008200802376139.PubMedCrossRefGoogle Scholar
  22. 22.
    Klawitter, M., Quero, L., Bertolo, A., Mehr, M., Stoyanov, J., Nerlich, A. G., et al. (2011). Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration. Journal Negative Results in Biomedicine, 29(10), 9. doi: 10.1186/1477-5751-10-9.CrossRefGoogle Scholar
  23. 23.
    Kim, J. S., Ellman, M. B., An, H. S., Yan, D., van Wijnen, A. J., Murphy, G., et al. (2012). Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc. Journal of Cellular Physiology, 227(4), 1512–1520. doi: 10.1002/jcp.22867.PubMedCrossRefGoogle Scholar
  24. 24.
    Yuan, H. Y., Tang, Y., Liang, Y. X., Lei, L., Xiao, G. B., Wang, S., et al. (2010). Matrix metalloproteinase-3 and vitamin d receptor genetic polymorphisms, and their interactions with occupational exposure in lumbar disc degeneration. International Journal of Occupational and Environmental Health, 52(1), 23–30.Google Scholar
  25. 25.
    Tallant, C., Marrero, A., & Gomis-Rüth, F. X. (2010). Matrix metalloproteinases: Fold and function of their catalytic domains. Biochimica et Biophysica Acta, 1803(1), 20–28. doi: 10.1016/j.bbamcr.2009.04.003.PubMedCrossRefGoogle Scholar
  26. 26.
    Genevay, S., Finckh, A., Mezin, F., Tessitore, E., & Guerne, P. A. (2009). Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation. Arthritis Research and Therapy, 11(6), R169. doi: 10.1186/ar2858.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Kang, Y. M., Choi, Y. R., Yun, C. O., Park, J. O., Suk, K. S., Kim, H. S., et al. (2013). Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from dupuytren nodule using adenovirus-mediated relaxin gene therapy. Journal of Orthopaedic Research,. doi: 10.1002/jor.22535.PubMedCentralGoogle Scholar
  28. 28.
    Hirt-Minkowski, P., Marti, H. P., Hönger, G., Grandgirard, D., Leib, S. L., Amico, P., et al. (2013). Correlation of serum and urinary matrix metalloproteases/tissue inhibitors of metalloproteases with subclinical allograft fibrosis in renal transplantation. Transplant Immunology,. doi: 10.1016/j.trim.2013.11.004.PubMedGoogle Scholar
  29. 29.
    Sun, Y., Yao, Y., & Ding, C. Z. (2013). A combination of sinomenine and methotrexate reduces joint damage of collagen induced arthritis in rats by modulating osteoclast-related cytokines. International Immunopharmacology,. doi: 10.1016/j.intimp.2013.11.014.PubMedCentralGoogle Scholar
  30. 30.
    Yaykasli, K. O., Turan, H., Kaya, E., & Hatipoglu, O. F. (2013). Polymorphisms in the promoters of MMP-2 and TIMP-2 genes in patients with acne vulgaris. International Journal of Clinical and Experimental Medicine, 6(10), 967–972.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Park, E. Y., & Park, J. B. (2013). Dose- and time-dependent effect of high glucose concentration on viability of notochordal cells and expression of matrix degrading and fibrotic enzymes. International Orthopaedics, 37(6), 1179–1186. doi: 10.1007/s00264-013-1836-2.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Vo, N. V., Hartman, R. A., Yurube, T., Jacobs, L. J., Sowa, G. A., & Kang, J. D. (2013). Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine Journal, 13(3), 331–341. doi: 10.1016/j.spinee.2012.02.027.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Haidong Xu
    • 1
  • Qiang Mei
    • 2
  • Jin He
    • 3
  • Gang Liu
    • 1
  • Jianning Zhao
    • 1
  • Bin Xu
    • 1
    Email author
  1. 1.Department of Orthopedics of Jinling HospitalNanjing University, School of MedicineNanjingChina
  2. 2.Department of Gastroenterology of the 169th Hospital, School of MedicineHunan Normal UniversityChangshaChina
  3. 3.Department of Neurosurgery of Jinling HospitalNanjing University, School of MedicineNanjingChina

Personalised recommendations