Coordinate regulation of IL-1beta and MMP-13 in rat tendons following subrupture fatigue damage.
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.
Sun
Hui B
HB
Leni and Peter May Department of Orthopaedics, Mount Sinai School of Medicine, 5 East 98th Street, 9th Floor, New York, NY 10029, USA.
Li
Yonghui
Y
Fung
David T
DT
Majeska
Robert J
RJ
Schaffler
Mitchell B
MB
Flatow
Evan L
EL
D000818:Animals; D001696:Biomechanical Phenomena; D012090:Cumulative Trauma Disorders / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000276:immunology; D017847:Patellar Ligament; D051381:Rats; D017207:Rats, Sprague-Dawley; D012421:Rupture; D052256:Tendinopathy / Q000235:genetics* / Q000276:immunology
D053583:Interleukin-1beta; D053509:Matrix Metalloproteinase 13