Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide
Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide
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DOI：
10.1152/japplphysiol.00131.2003
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发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Guilak, F
中科院分区：
文献类型：
--
作者：
Shin, SJ;Fermor, B;Guilak, F
半月板是一种关节内纤维软骨结构，在膝关节中起着重要的生物力学作用。损伤或关节炎时，半月板可能暴露在生化和生物力学环境的显著变化中，这可能导致关节疾病的进展。本研究的目的是研究在白细胞介素-1 （IL-1）存在的情况下，机械应力对半月板基质转换的影响，并确定一氧化氮（NO）在这些过程中的作用。将猪半月板外植体置于0.1 MPa、0.5 Hz、1 ng/ml IL-1的动态压缩应力下24 h，测定其总蛋白、蛋白聚糖和NO的合成。测定了一种一氧化氮合酶2 （NOS2）抑制剂的作用。与未压缩外植体相比，动态压缩显著提高了蛋白质和蛋白多糖的合成，分别提高了68%和58%。IL-1的存在阻止了机械应力的这种刺激作用，但通过特异性抑制NOS2恢复了这种刺激作用。通过IL-1或机械压缩，蛋白聚糖向培养基中的释放增加，并通过IL-1和机械压缩进一步增强。无论IL-1是否存在，蛋白聚糖释放对压缩的刺激都依赖于NOS2。这些发现表明，IL-1可能通过依赖于NO的途径调节机械应力对细胞外基质周转的影响。
The 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.