Cook Alex E, Cook James L, Stoker Aaron M
School of Medicine, Kansas City University of Medicine and Biosciences, Kansas City, Missouri.
Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri.
J Knee Surg. 2018 Oct;31(9):834-840. doi: 10.1055/s-0037-1615821. Epub 2018 Jan 2.
This article identifies the potential mechanisms of action for meniscal degeneration in response to joint inflammation and potential contributions of the meniscus to the development and progression of osteoarthritis (OA). It was hypothesized that interleukin-1β (IL-1β) stimulation of meniscal explants would result in significant increases in nitric oxide (NO), matrix metalloproteinase (MMP) production and activity, and relevant cytokine production compared with controls. Canine meniscal explants (4 mm) were cultured for 21 days with (IL-1) or without (negative control [NC]) 50 ng/mL rcIL-1β ( = 6/group). Media were changed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, NO, prostaglandin E (PGE2), IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and keratinocyte-derived chemokine (KC) concentrations. Media NO and PGE2 concentrations were significantly higher in the IL-1 group at all time points except for days 9 and 12. The concentrations of MMP-13 were significantly higher in the IL-1 group at days 3, 6, 9, and 12. The production of MMP-2 was significantly lower in the IL-1 group on days 3 through 15. ADAMTS4 activity was significantly higher in the IL-1 group on days 6 through 18. MMP-3 concentrations and general MMP activity were significantly higher in the IL-1 group at all time points. Concentrations of IL-6, IL-8, MCP-1, and KC were significantly higher in the IL-1 group at most time points. Glycosaminoglycans (GAG) content decreased significantly ( = 0.009) in the IL-1 group compared with the NC group. Proinflammatory mediators appear to directly influence degradative processes in the meniscus, which in turn contribute to development and progression of OA by production of proinflammatory and degradative mediators. These findings have important clinical implications for the management of the degenerative meniscus and the osteoarthritic knee.
本文确定了半月板退变对关节炎症反应的潜在作用机制，以及半月板对骨关节炎（OA）发生和发展的潜在影响。研究假设，与对照组相比，白细胞介素-1β（IL-1β）刺激半月板外植体将导致一氧化氮（NO）、基质金属蛋白酶（MMP）的产生和活性以及相关细胞因子的产生显著增加。将犬半月板外植体（4毫米）在含有（IL-1）或不含有（阴性对照[NC]）50纳克/毫升重组人IL-1β（每组n = 6）的条件下培养21天。每3天更换一次培养基，并分析MMP活性、含血小板解聚蛋白样金属蛋白酶-4（ADAMTS-4）活性、MMP-1、MMP-2、MMP-3、MMP-9、MMP-13、NO、前列腺素E（PGE2）、IL-6、IL-8、单核细胞趋化蛋白-1（MCP-1）和角质形成细胞衍生趋化因子（KC）的浓度。除第9天和第12天外，IL-1组在所有时间点的培养基NO和PGE2浓度均显著更高。在第3、6、9和12天，IL-1组的MMP-13浓度显著更高。在第3至15天，IL-1组的MMP-2产生显著更低。在第6至18天，IL-1组的ADAMTS4活性显著更高。在所有时间点，IL-1组的MMP-3浓度和总体MMP活性均显著更高。在大多数时间点，IL-1组的IL-6、IL-8、MCP-1和KC浓度显著更高。与NC组相比，IL-1组的糖胺聚糖（GAG）含量显著降低（P = 0.009）。促炎介质似乎直接影响半月板的降解过程，进而通过产生促炎和降解介质促进OA的发生和发展。这些发现对退变半月板和骨关节炎膝关节的治疗具有重要的临床意义。
