Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide

Abstract

. Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide. J Appl Physiol 95: 308-313, 2003. First published March 28, 2003 10.1152/ japplphysiol.00131.2003The meniscus is an intra-articular fibrocartilaginous structure that serves essential biomechanical roles in the knee. With injury or arthritis, the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likely contribute to the progression of joint disease. The goal of this study was to examine the influence of mechanical stress on matrix turnover in the meniscus in the presence of interleukin-1 (IL-1) and to determine the role of nitric oxide (NO) in these processes. Explants of porcine menisci were subjected to dynamic compressive stresses at 0.1 MPa for 24 h at 0.5 Hz with 1 ng/ml IL-1, and the synthesis of total protein, proteoglycan, and NO was measured. The effects of a nitric oxide synthase 2 (NOS2) inhibitor were determined. Dynamic compression significantly increased protein and proteoglycan synthesis by 68 and 58%, respectively, compared with uncompressed explants. This stimulatory effect of mechanical stress was prevented by the presence of IL-1 but was restored by specifically inhibiting NOS2. Release of proteoglycans into the medium was increased by IL-1 or mechanical compression and further enhanced by IL-1 and compression together. Stimulation of proteoglycan release in response to compression was dependent on NOS2 regardless of the presence of IL-1. These finding suggest that IL-1 may modulate the effects of mechanical stress on extracellular matrix turnover through a pathway that is dependent on NO.

Inhibition of Matrix Metalloproteinases Enhances In Vitro Repair of the Meniscus

“…In meniscal explants, static loading decreases biosynthesis of matrix components [30] and increases expression of MMPs [52]. Conversely, dynamic compression or stretch increase matrix biosynthesis [20,51] and can decrease the inflammatory effects of IL-1 on isolated meniscal cells by blocking MMP-13 mRNA upregulation [21]. Ultimately, a combination of MMP inhibition, anabolic growth factors, and/or physical factors, such as mechanical loading, probably will be most beneficial for enhancing integrative meniscal repair.…”

Region-specific constitutive gene expression in the adult porcine meniscus

“…47,48 In addition, the inner regions of the meniscus expressed mRNA for the pro-inflammatory enzyme NOS2 at significantly higher levels than the outer region. Previous work has implicated this enzyme in the production of nitric oxide following partial meniscectomy 49 and exposure to mechanical stimuli, 28,29,31 which in turn, may regulate meniscus cell biosynthesis. It has been suggested that the rounded cells of the central and inner regions of the meniscus may be responsible for the synthesis of nitric oxide.…”

Anti‐inflammatory effects of continuous passive motion on meniscal fibrocartilage

“…Interleukin-1 (IL-1), a major mediator, induces proinflammatory mediators, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) and triggers the pathologies of the cartilage and fibrocartilage associated with RA [1,13]. Both chondrocytes and fibrochondrocytes from inflamed joints are known to produce proinflammatory mediators in response to IL-1 in vitro [1,18] and in vivo [11].…”