Clinical Orthopaedics and Related Research

, Volume 466, Issue 7, pp 1555–1561

Coordinate Regulation of IL-1β and MMP-13 in Rat Tendons Following Subrupture Fatigue Damage

  • Hui B. Sun
  • Yonghui Li
  • David T. Fung
  • Robert J. Majeska
  • Mitchell B. Schaffler
  • Evan L. Flatow
Symposium: Molecular and Clinical Developments in Tendinopathy

DOI: 10.1007/s11999-008-0278-4

Cite this article as:
Sun, H.B., Li, Y., Fung, D.T. et al. Clin Orthop Relat Res (2008) 466: 1555. doi:10.1007/s11999-008-0278-4

Abstract

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-1β. 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-1β. In vivo fatigue loading at 1.7% strain caused overt microstructural damage and upregulated expression of MMP-13 and IL-1β, while 0.6% strain produced only minor changes in matrix microstructure and downregulated expression of both MMP-13 and IL-1β. 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-1β 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-1β in tendons in vivo and tenocytes in vitro in a load-dependent manner. The data also suggest MMP-13 is regulated by both IL-1β-dependent and IL-1β-independent pathways.

Copyright information

© The Association of Bone and Joint Surgeons 2008

Authors and Affiliations

  • Hui B. Sun
    • 1
  • Yonghui Li
    • 1
  • David T. Fung
    • 1
  • Robert J. Majeska
    • 1
  • Mitchell B. Schaffler
    • 1
  • Evan L. Flatow
    • 1
  1. 1.Leni and Peter May Department of OrthopaedicsMount Sinai School of MedicineNew YorkUSA