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

Hui (Herb) Sun, Yonghui Li, David T. Fung, Robert J. Majeska, Mitchell B. Schaffler, Evan L. Flatow

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1555-1561
Number of pages7
JournalClinical Orthopaedics and Related Research
Volume466
Issue number7
DOIs
StatePublished - Jul 2008
Externally publishedYes

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Matrix Metalloproteinases
Interleukin-1
Tendons
Fatigue
Tendinopathy
Patellar Ligament
Hydrostatic Pressure
Small Interfering RNA
Down-Regulation
Cytokines
Messenger RNA
Enzymes
Genes
Tenocytes

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Coordinate regulation of IL-1β and MMP-13 in rat tendons following subrupture fatigue damage. / Sun, Hui (Herb); Li, Yonghui; Fung, David T.; Majeska, Robert J.; Schaffler, Mitchell B.; Flatow, Evan L.

In: Clinical Orthopaedics and Related Research, Vol. 466, No. 7, 07.2008, p. 1555-1561.

Research output: Contribution to journalArticle

Sun, Hui (Herb) ; Li, Yonghui ; Fung, David T. ; Majeska, Robert J. ; Schaffler, Mitchell B. ; Flatow, Evan L. / Coordinate regulation of IL-1β and MMP-13 in rat tendons following subrupture fatigue damage. In: Clinical Orthopaedics and Related Research. 2008 ; Vol. 466, No. 7. pp. 1555-1561.
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