Despite increasing evidence that meniscal degeneration is an early event in the development of knee osteoarthritis, relatively little is known regarding the sequence or functional implications of cytokine-induced meniscal degradation or how degradation varies with age. This study examined dose-dependent patterns of interleukin-1 (IL-1)-induced matrix degradation in explants from the radially middle regions of juvenile and adult bovine menisci. Tissue explants were cultured for 10 days in the presence of 0, 1.25, 5, or 20 ng/ml recombinant human IL-1a. Juvenile explants exhibited immediate and extensive sulfated glycosaminoglycan (sGAG) loss and subsequent collagen release beginning after 4-6 days, with relatively little IL-1 dose-dependence. Adult explants exhibited a more graded response to IL-1, with dose-dependent sGAG release and a lower fraction of sGAG released (but greater absolute release) than juvenile explants. In contrast to juvenile explants, adult explants exhibited minimal collagen release over the 10-day culture. Compressive and shear moduli reflected the changes in explant composition, with substantial decreases for both ages but a greater relative decrease in juvenile tissue. Dynamic moduli exhibited stronger dependence on explant sGAG content for juvenile tissue, likely reflecting concomitant changes to both proteoglycan and collagen tissue components. The patterns of tissue degradation suggest that, like in articular cartilage, meniscal proteoglycans may partially protect collagen from cell-mediated degeneration. A more detailed view of functional changes in meniscal tissue mechanics with degeneration will help to establish the relevance of in vitro culture models and will advance understanding of how meniscal degeneration contributes to overall joint changes in early stage osteoarthritis. Keywords: meniscus; degeneration; interleukin-1; biomechanics; composition-function Although associations of meniscal degeneration with knee osteoarthritis (OA) have long been suspected, 1 little is known about the specific contributions of degenerative meniscal changes to OA pathogenesis. Meniscal tears have long been recognized as contributing factors to the progression of knee OA due to changes in tibiofemoral contact biomechanics 2,3 and altered joint kinematics. 4 Magnetic resonance imaging (MRI) studies have indicated that degenerative meniscal lesions without macroscopic tearing are associated with increased meniscal extrusion and with the progression of OA, 5-7 implying that meniscal degeneration substantially alters the biomechanical functions of menisci. Degenerative meniscal lesions have been found not only in patients diagnosed with early OA 8 but also in an asymptomatic control population, with incidence increasing with age in both genders. 9 Both visual and MRI evidence of meniscal changes were found to precede evidence of cartilage changes, 1,9 strongly implying that meniscal degeneration may be a precursor to the development of advanced knee OA. Understanding the mechanisms of menis...

Despite a growing recognition that meniscal degeneration often precedes cartilage degeneration in the development of knee osteoarthritis (OA), little is known about the role of meniscal degeneration in the onset and progression of knee OA. Even a mild degenerative lesion increases meniscal extrusion, implying changes in biomechanical function. Understanding the mechanisms of meniscal degeneration may enable the diagnosis and disease-modifying treatment of early knee OA, potentially preventing or slowing the progression of the disease. The roles of pro-inflammatory cytokines such as interleukin-1 (IL-1) in promoting cartilage matrix degradation and mediating inflammation in the progression of OA have been widely demonstrated [1,2]. Recent results from our group indicated that 20ng/ml hrIL-1α produced similar cell-mediated degradation and loss of mechanical properties in immature cartilage and meniscus, but progresses more rapidly in meniscus explants [3]. This study further explored the effects of IL-1α dosage and medial-lateral differences on the functional degradation of meniscal explants.