Coordinate regulation of IL-1beta and MMP-13 in rat tendons following subrupture fatigue damage

Clin Orthop Relat Res. 2008 Jul;466(7):1555-61. doi: 10.1007/s11999-008-0278-4. Epub 2008 May 10.


Mechanical overloading is a major causative factor of tendinopathy; however, its underlying mechanisms are unclear. We hypothesized mechanical overloading would damage tendons and alter genes associated with tendinopathy in a load-dependent manner. To test this hypothesis, we fatigue loaded rat patellar tendons in vivo and measured expression of the matrix-degrading enzyme MMP-13 and the inflammatory cytokine IL-1beta. We also examined these responses in cultured tenocytes exposed to intermittent hydrostatic pressure in vitro. Additionally, we hypothesized load-induced changes in tenocyte MMP-13 expression would be dependent on expression of IL-1beta. In vivo fatigue loading at 1.7% strain caused overt microstructural damage and upregulated expression of MMP-13 and IL-1beta, while 0.6% strain produced only minor changes in matrix microstructure and downregulated expression of both MMP-13 and IL-1beta. Loading of cultured tenocytes at 2.5 and 7.5 MPa produced comparable changes in expression to those of in vivo tendon loading. Blocking IL-1beta expression with siRNA suppressed load-induced both MMP-13 mRNA expression and activity. The data suggest fatigue loading alters expression of MMP-13 and IL-1beta in tendons in vivo and tenocytes in vitro in a load-dependent manner. The data also suggest MMP-13 is regulated by both IL-1beta-dependent and IL-1beta-independent pathways.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Cumulative Trauma Disorders / genetics
  • Cumulative Trauma Disorders / immunology
  • Disease Models, Animal
  • Female
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / immunology
  • Matrix Metalloproteinase 13 / genetics*
  • Matrix Metalloproteinase 13 / immunology
  • Patellar Ligament
  • Rats
  • Rats, Sprague-Dawley
  • Rupture
  • Tendinopathy / genetics*
  • Tendinopathy / immunology


  • Interleukin-1beta
  • Matrix Metalloproteinase 13