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.
One or more of the authors (HBS, MBS, ELF) has received funding from the National Institutes of Health. This study was supported
by grants from the Aircast Foundation and NIH Grants AR41210, AR52743, and AR50968.
Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations
were conducted in conformity with ethical principles of research.