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

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

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

“…The up‐regulation of MMP‐3 and MMP‐13 in the current study also agrees with previous work, showing up‐regulation of both these MMPs in pathological tendons 45, 47, 48, 49, 50. However, MMP‐3 has also been shown to be down‐regulated in both ruptured and tendinopathic tendons, as shown by the mRNA expression level 46.…”

J. Leonard Goldner Award 2008: Effect of Extracorporeal Shock Wave Therapy on Cultured Tenocytes

“…MMPs and ILs are markers of tendinopathy and may have a role in the pathomechanics of tendinopathy. 2,15,17,18 These preliminary findings suggest a mechanism of action of shock wave treatment and may partially indicate the reason shock wave treatment works clinically. The findings call into question other theories of shock wave mechanism of action based on adverse effect on cells.…”

Efeito do laser de baixa potência (810 nM) na tendinite induzida por colagenase em tendão calcâneo de ratos.

“…Além da sobrecarga mecânica conhecida como o principal fator causador dessas tendinopatias existem processos lesivos repentinos e o envelhecimento que também contribuem para a degeneração do tendão que pode ocorrer na ausência (tendinose) ou na presença (tendinite) de resposta inflamatória (SUN et al, 2008).…”

“…Uma das formas do tecido tendíneo responder a doença é alterando a expressão de algumas enzimas de degradação, como colagenases e citocinas inflamatórias que pode levar à degeneração do tecido e a perda da integridade mecânica (NAKAMA et al, 2006;SCOTT A et al, 2007;SUN et al, 2008).…”

“…Desta forma, a supressão de algumas MMPs poderia auxiliar no reparo do tendão (UEDA et al, 2008). Tanto no ser humano como em outros animais com tendinopatias, a MMP-13 poderia apresentar uma ação comparável a MMP-1, e seu aumento poderia significar uma maior degradação da matriz extracelular (SUN et al, 2008).…”