Skip to main content

Advertisement

SpringerLink
Log in

MMP-1, IL-1β, and COX-2 mRNA Expression is Modulated by Static Load in Rabbit Flexor Tendons

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Tendon cells respond to their mechanical environment by synthesizing and degrading the surrounding matrix. This study examined how expression of genes associated with tendon degeneration is affected by static loads. Forty flexor tendons from 10 New Zealand White rabbits were harvested and secured in a tissue loading system. A static load of 0, 2, 4, or 6 MPa was applied to tendons for 20 h. MMP-1, IL-1β, COX-2, GAPDH, and 18s mRNA expression was measured by qRT-PCR. MMP-1 expression in tendons loaded to 6 MPa was significantly increased 259% compared to tendons loaded to 4 MPa. Relative to a 0 MPa load, IL-1β expression was inhibited with load at 4 MPa (48%) while COX-2 expression was increased at 6 MPa (219%). A polynomial regression analysis found a significant positive correlation between creep and expression of MMP-1 (R 2 = 0.53, p < 0.001) and IL-1β (R 2 = 0.55, p < 0.001). The results of this study indicate that moderate load inhibits IL-1β and high load stimulates COX-2 relative to stress shielding. MMP-1 expression is up-regulated with high loads compared to moderate loads. The correlation between creep and expression suggests that the pathway for MMP-1 and IL-1β expression, leading eventually to tendon degeneration, may be regulated by the biomechanical factor creep.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Abiko Y., N. Shimizu, M. Yamaguchi, H. Suzuki, H. Takiguchi. Effect of aging on functional changes of periodontal tissue cells. Ann. Periodontol. 3: 350–369, 1998

    PubMed  CAS  Google Scholar 

  2. Archambault J. M., M. Tsuzaki, W. Herzog, A. Banes. Stretch and interleukin-1beta induce matrix metalloproteinases in rabbit tendon cells in vitro. J. Orthop. Res. 20(1): 36–39, 2002

    Article  PubMed  CAS  Google Scholar 

  3. Archambault J. M., J. P. Wiley, R. C. Bray. Exercise loading of tendons and the development of overuse injuries. A review of current literature. Sports Med. 20(2): 77–89, 1995

    Article  PubMed  CAS  Google Scholar 

  4. Arnoczky S., T. Tian, M. Lavagnino, K. Gardner. Ex vivo static tensile loading inhibits MMP-1 expression in rat tail tendon cells through a cytoskeletally based mechanotransduction mechanism. J. Orthop. Res. 22(2): 328–333, 2004

    Article  PubMed  CAS  Google Scholar 

  5. Asundi, K., K. Kursa, J. Lotz, and D. Rempel. In vitro system for applying cyclic loads to connective tissues under force or displacement control. Ann. Biomed. Eng. 35:1188–1195, 2007

    Google Scholar 

  6. Banes A., M. Tsuzaki, J. Yamamoto, T. Fischer, B. Brigman, T. Brown, L. Miller. Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem. Cell Biol. 73: 349–365, 1995

    Article  PubMed  CAS  Google Scholar 

  7. Banes A. J., P. Weinhold, X. Yang, M. Tsuzaki, D. Bynum, M. Bottlang, T. Brown. Gap junctions regulate response of tendon cells ex vivo to mechanical loading. Clin. Orthop. Relat. Res. 367: s356–s370, 1999

    Article  PubMed  Google Scholar 

  8. Bankers-Fulbright J., K. Kalli, K. McKean. Interleukin-1 signal transduction. Life Sci. 59: 61–83, 1996

    Article  PubMed  CAS  Google Scholar 

  9. Bernard, B. Musculoskeletal disorders and workplace factors. NIOSH Publication 97-141, 1997

  10. Butler D., E. Grood, F. R Noyes, R. F. Zernicke, K. Brackett. Effects of structure and strain measurement technique on the material properties of young human tendons and fascia. J. Biomech. 17(8): 579–596, 1984

    Article  PubMed  CAS  Google Scholar 

  11. Gillroy D. W., A. Tomlinson, D. A. Willoughby. Differential effects of inhibition of isoforms of cyclooxygenase (COX1, COX2) in chronic inflammation. Inflamm. Res. 47: 79–85, 1998

    Article  Google Scholar 

  12. Goldstein S. A., T. J. Armstrong, D. B. Chaffin, L. S. Matthews. Analysis of cumulative strain in tendons and tendon sheaths. J. Biomech. 20: 1–6, 1987

    Article  PubMed  CAS  Google Scholar 

  13. Hannafin J. A., S. P. Arnoczky, A. Hoonjan, P. A. Torzilli. Effect of stress deprivation and cyclic tensile loading on material and morphological properties of canine flexor digitorum profundus tendon: an in vitro study. J. Orthop. Res. 13: 907–914, 1995

    Article  PubMed  CAS  Google Scholar 

  14. Hanson K., J. Weiss, J. Barton. Recruitment of tendon crimp with applied tensile strain. J. Biomech. Eng. 124: 72–77, 2002

    Article  Google Scholar 

  15. Ireland D., R. Harral, V. Curry, G. Holloway, R. Hackney, B. Hazleman, G. Riley. Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol. 20: 159–169, 2001

    Article  PubMed  CAS  Google Scholar 

  16. Jozsa, L., and P. Kannus. In: Human Tendons: Anatomy, Physiology and Pathology. Champaign: Human Kinetics, 1997

  17. Koshima H., S. Kondo, S. Mishima, H. R. Choi, H. Shimpo, T. Sakai, N. Ishiguro. Expression of interleukin-1beta, cyclooxygenase-2, and prostaglandin E2 in a rotator cuff tear in rabbits. J. Orthop. Res. 25: 92–97, 2007

    Article  PubMed  CAS  Google Scholar 

  18. Lavagnino M., S. P. Arnoczky. In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells. J. Orthop. Res. 23(5): 1211–1218, 2005

    Article  PubMed  CAS  Google Scholar 

  19. Lavagnino M., S. P. Arnoczky, M. Egerbacher, K. L. Gardner, M. E. Burns. Isolated fibrillar damage in tendons stimulates local collagenase mRNA expression and protein synthesis. J. Biomech. 39: 2355–2362, 2006

    Article  PubMed  Google Scholar 

  20. Lavignino M., S. P. Arnoczky, T. Tian, Z. Vaupel. Effect of amplitude and frequency of cyclic tensile stress on the inhibition of MMP-1 mRNA expression in tendon cells: an in vitro study. Connect. Tissue Res. 44: 181–187, 2003

    Article  Google Scholar 

  21. Majima T., L. L. Marchuk, N. G. Shrive, C. B. Frank, D. A. Hart. In-vitro cyclic tensile loading of an immobilized and mobilized ligament autograft selectively inhibits mRNA levels for collagenase (MMP-1). J. Orthop. Sci. 5(5): 503–510, 2000

    Article  PubMed  CAS  Google Scholar 

  22. Malaviya P., D. Butler, D. Korvick, F. Proch. In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model. J. Biomech. 31:1043–1049, 1998

    Article  PubMed  CAS  Google Scholar 

  23. Mansur N. R., K. Meyer-Siegler, J. C. Wurzer, M. A. Sirover. Cell cycle regulation of the glyceraldehyde-3-phosphate dehydrogenase/uracil DNA glycosylase gene in normal human cells. Nucleic Acid Res. 21(4): 993–998, 1993

    Article  PubMed  CAS  Google Scholar 

  24. Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. TIG 6: 121–125, 1990

    PubMed  CAS  Google Scholar 

  25. Narumiya S., Y. Sugimoto, F. Ushikubi. Prostanoid receptors: structures, properties, and functions. Physiol. Rev. 79: 1193–1226, 1999

    PubMed  CAS  Google Scholar 

  26. Okuda Y., J. P. Gorski, K. N. An, P. C. Amadio. Biochemical, histological and biomechanical analyses of canine tendon. J. Orthop. Res. 5: 60–68, 1987

    Article  PubMed  CAS  Google Scholar 

  27. Perry S., S. McIlhenny, M. Hoffman, L. Soslowsky. Inflammatory and angiogenic mRNA levels are altered in a supraspinatus tendon overuse animal model. J. Shoulder Elbow Surg. 14(1 Suppl S): 79S–83S, 2005

    Article  PubMed  Google Scholar 

  28. Riley G. P., V. Curry, J. DeGroot, B. van El, N. Verzijl, B. L. Hazleman, R. A. Bank. Matrix metalloproteinase activities and their relationship with collagen remodeling in tendon pathology. Matrix Biol. 21: 185–195, 2002

    Article  PubMed  CAS  Google Scholar 

  29. Screen H., D. Lee, D. Bader, J. Shelton. An investigation into the effects of the hierarchical structure of tendon fascicles on micromechanical properties. Proc. Inst. Mech. Eng. [H] 218(2): 109–119, 2004

    CAS  Google Scholar 

  30. Slack C., M. H. Flint, B. M. Thompson. The effect of tensional load on isolated embryonic chick tendons in organ culture. Connect. Tissue Res. 12: 229–247, 1984

    Article  PubMed  CAS  Google Scholar 

  31. Thornton G. M., N. G. Shrive, C. B. Frank. Ligament creep recruits fibres at low stresses and can lead to modulus-reducing fibre damage at higher creep stresses: a study in rabbit medial collateral ligament model. J. Orthop. Res. 20(5): 967–974, 2002

    Article  PubMed  CAS  Google Scholar 

  32. Tsuzaki M., D. Bynum, L. Almekinders, X. Yang, J. Faber, A. J. Banes. ATP modulates load-inducible IL-1 beta, COX 2, and MMP-3 gene expression in human tendon cells. J. Cell Biochem. 89(3): 556–562, 2003

    Article  PubMed  CAS  Google Scholar 

  33. Tsuzaki M., G. Guyton, W. Garrett, J. M. Archambault, W. Herzog, L. Almekinders, D. Bynum, X. Yang, A. J. Banes. IL-1 beta induces COX2, MMP-1, -3 and -13, ADAMTS-4, IL-1 beta and IL-6 in human tendon cells. J. Orthop. Res. 21(2): 256–264, 2003

    Article  PubMed  CAS  Google Scholar 

  34. Uchida H., H. Tohyama, K. Nagashima, Y. Ohba, H. Matsumoto, Y. Toyama, K. Yasuda. Stress deprivation simultaneously induces over-expression of interleukin-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta in fibroblasts and mechanical deterioration of the tissue in the patellar tendon. J. Biomech. 38: 791–798, 2005

    Article  PubMed  Google Scholar 

  35. Wang J. H. Mechanobiology of tendons. J. Biomech. 39: 1563–1582, 2006

    Article  PubMed  Google Scholar 

  36. Wang J. H., F. Jia, G. Yang, S. Yang, B. Campbell, D. Stone, S. L. Woo. Cyclic mechanical stretching of human tendon fibroblasts increases the production of prostaglandin E2 and levels of cyclooxygenase expression: a novel in vitro model study. Connect. Tissue Res. 44: 128–133, 2003

    Article  PubMed  CAS  Google Scholar 

  37. Wang X., R. F. Ker. Creep rupture of wallaby tail tendons. J. Exp. Biol. 198: 831–845, 1995

    PubMed  CAS  Google Scholar 

  38. Wang X., R. F. Ker, R. M. Alexander. Fatigue rupture of wallaby tail tendons. J. Exp. Biol. 198: 847–852, 1995

    PubMed  CAS  Google Scholar 

  39. Wren T. A., D. P. Lindsey, G. S. Beaupre, D. R. Carter. Effects of creep and cyclic loading on the mechanical properties and failure of human Achilles tendons. Ann. Biomed. Eng. 31: 710–717, 2003

    Article  PubMed  Google Scholar 

  40. Yang G., H. J. Im, J. H. Wang. Repetitive mechanical stretching modulates IL-1 beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene 363: 166–172, 2005

    Article  PubMed  CAS  Google Scholar 

  41. Zernicke R. F., D. L. Butler, E. S. Grood, M. S. Hefzy. Strain topography of human tendon and fascia. J. Biomech. Eng. 106: 177–180, 1984

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Funding for this study was provided by the Centers for Disease and Prevention, National Institute for Occupational Safety and Health Training Grant.

Author information

Authors and Affiliations

  1. Ergonomics Program, Department of Bioengineering, University of California, Berkeley, 1301 South 46th Street, Building 163, Richmond, CA, 94804, USA

    Krishna R. Asundi & David M. Rempel

Authors
  1. Krishna R. Asundi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Rempel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David M. Rempel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asundi, K.R., Rempel, D.M. MMP-1, IL-1β, and COX-2 mRNA Expression is Modulated by Static Load in Rabbit Flexor Tendons. Ann Biomed Eng 36, 237–243 (2008). https://doi.org/10.1007/s10439-007-9427-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-007-9427-2

Keywords

Search

Navigation