Repetitive mechanical stretching modulates IL-1β induced COX-2, MMP-1 expression, and PGE 2 production in human patellar tendon fibroblasts

Abstract

While mechanical loading is known to be essential in maintaining tendon homeostasis, repetitive mechanical loading has also been implicated in the etiology of tendon overuse injuries. The purpose of this study was to determine whether cyclic mechanical stretching regulates inflammatory responses induced by interleukin-1β (IL-1β) treatment in human patellar tendon fibroblasts (HPTFs). HPTFs were grown in microgrooved silicone dishes, where they became elongated in shape and aligned with the microgrooves, which is similar to the shape and organization of tendon fibroblasts in vivo. Cyclic uniaxial stretching was then applied to silicone culture dishes with a 4% or 8% stretch at a stretching frequency of 0.5 Hz for a duration of 4 h in the presence or absence of 10 pM IL-1β treatment. Non-stretched cells in the presence or absence of IL-1β were used for controls, respectively. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), and the production of prostaglandin E 2 (PGE 2) were measured. In the absence of stretching, it was found that 10 pM of IL-1β markedly induced higher levels of COX-2, MMP-1 gene expression, and PGE 2 production than non-treated cells. Furthermore, cells with 4% stretching decreased the COX-2 and MMP-1 gene expression and PGE 2 production that were stimulated by IL-1β, whereas cells with 8% stretching further increased these gene products and/or expression levels in addition to the effects of IL-1β stimulation. Thus, the results suggest that repetitive, small-magnitude stretching is anti-inflammatory, whereas large-magnitude stretching is pro-inflammatory. Therefore, moderate exercise may be beneficial to reducing tendon inflammation.