Dynamic biophysical strain modulates proinflammatory gene induction in meniscal fibrochondrocytes

Abstract

Fibrochondrocytes of meniscus adapt to changes in their biomechanical environment by mechanisms that are yet to be elucidated. In this study, the mechanoresponsiveness of fibrochondrocytes under normal and inflammatory conditions was investigated. Fibrochondrocytes from rat meniscus were exposed to dynamic tensile forces (DTF) at various magnitudes and frequencies. The mechanoresponsiveness was assessed by examining the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-13 mRNA expression. The mRNA and protein analyses revealed that DTF at magnitudes of 5% to 20% did not induce proinflammatory gene expression. IL-1β induced a rapid increase in the iNOS mRNA. DTF strongly repressed IL-1β-dependent iNOS induction in a magnitude-dependent manner. Exposure to 15% DTF resulted in >90% suppression of IL-1β-induced mRNA within 4 h and this suppression was sustained for the ensuing 20 h. The mechanosensitivity of fibrochondrocytes was also frequency dependent and maximal suppression of iNOS mRNA expression was observed at rapid frequencies of DTF compared with lower frequencies. Like iNOS, DTF also inhibited IL-1β-induced expression of proinflammatory mediators involved in joint inflammation. The examination of temporal effects of DTF revealed that 4- or 8-h exposure of DTF was sufficient for its sustained anti-inflammatory effects during the next 20 or 16 h, respectively. Our findings indicate that mechanical signals act as potent anti-inflammatory signals, where their magnitude and frequency are critical determinants of their actions. Furthermore, mechanical signals continue attenuating proinflammatory gene transcription for prolonged periods of time after their removal.