Stretch and interleukin‐1β induce matrix metalloproteinases in rabbit tendon cells in vitro

Abstract Little is known about the factors that initiate and propagate tendon overuse injuries, but chronic inflammation and matrix destruction have been implicated. The purpose of this study was to evaluate the production of cyclooxygenase II (COX‐2) and matrix metalloproteinases (MMPs) by tendon cells exposed to cyclic strain and inflammatory cytokines in vitro. Rabbit Achilles tendon cells were subjected to a stretching protocol with 5% elongation at 0.33 Hz for 6 h, or treated with 1000 pM interleukin‐1β (IL‐1β), or exposed to IL‐1β and stretching together. Gene expression was evaluated by RT‐PCR and production of stromelysin was quantified with an ELISA. IL‐1β induced the expression of the collagenase‐1 and stromelysin‐1 genes. Production of stromelysin proenzyme by cells stimulated with IL‐1β was 17 times higher than production by control cells. Cells exposed to IL‐1β and stretching produced 20 times more stromelysin than control cells. Cells subjected to stretching alone did not produce more stromelysin than control cells. The synergistic effect of IL‐1β and stretching was observed at doses of IL‐1β ranging from 10 to 1000 pM. These data suggest that mechanical load and inflammatory cytokines can initiate a matrix destructive pathway in tendon that is more pronounced than with mechanical loading or inflammation alone. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.