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Coordinate regulation of IL-1beta and MMP-13 in rat tendons following subrupture fatigue damage.| Authors: | Hui B Sun, Yonghui Li, David T Fung, Robert J Majeska, Mitchell B Schaffler, Evan L Flatow | | Language: | Eng. | | Date: | 11-06-2008 | | Journal: | Clinical orthopaedics and related research
(1528-1132)
| | Release: | Clin Orthop Relat Res. 2008 Jul;466(7):1555-61 | |
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Abstract:
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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.
| | Copyright: | Clinical orthopaedics and related research
Leni and Peter May Department of Orthopaedics, Mount Sinai School of Medicine, 5 East 98th Street, 9th Floor, New York, NY 10029, USA. | | Full text: |  EBSCO - HTML (needs subscription) | | Terms: | Animals, Biomechanics, Cumulative Trauma Disorders, Disease Models, Animal, Female, Interleukin-1beta, Matrix Metalloproteinase 13, Patellar Ligament, Rats, Rats, Sprague-Dawley, Rupture, Tendinopathy | | |
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