ROLE OF IL-1 ON AGGRECANASE AND COX-2 GENE EXPRESSION OF MENISCAL EXPLANTS FOLLOWING DYNAMIC COMPRESSION

摘要

The menisci within the knee likely respond to adverse loading conditions, leading to aggravated cartilage damage and fissuring [1]. Upregulation of catabolic molecules such as interleukin-1α (IL-1α), metalloproteinases (MMPs), aggrecanases (ADAMTS-4 and -5), and cyclooxygenase-2 (COX-2), as well as release of proteoglycans [2], have been shown in vitro for meniscal explants following dynamic loading [3]. A crucial event in matrix degradation is the loss of aggrecan, caused by the ADAMTS family [4]. In osteoarthritic cartilage, IL-1 has been shown to influence COX-2 activity, leading to increased synthesis of prostaglandin E2 and subsequent proteinase activity [5]. Increased compressive stresses and strains likely lead to changes in the transcriptional response of fibrocartilaginous tissues in vitro, specifically IL-1 [6]. Inhibiting the catabolic IL-1 pathway induced by mechanical loading could potentially provide therapeutic benefits following traumatic injury. Organisms naturally control activation of IL-1 signaling via IL-1 receptor antagonist (IL-1RA). Previously, we have shown that blocking IL-1 via IL-1RA leads to decreased MMP expression [7]. However, the role of IL-1 on the expression of aggrecanases and COX-2 in the meniscus is not well understood. We hypothesized that IL-1, which is influenced by varying compressive loading on the meniscus, induces a catabolic cascade of aggrecanase and cyclooxygenase gene expression. Thus, by inhibiting IL-1 activity, we predicted that catabolic gene expression in meniscal tissue would be reduced following high dynamic strains.