Wang J, Elewaut D, Hoffman I, Veys E M, Verbruggen G
Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
Ann Rheum Dis. 2004 Jan;63(1):61-6. doi: 10.1136/ard.2002.005298.
To investigate the effects of physiological doses of hydrocortisone on synthesis and turnover of cell associated matrix (CAM) by human chondrocytes obtained from normal articular cartilage.
Human articular cartilage cells were obtained from visually intact cartilage of the femoral condyles of five donors and maintained in culture for one week to reach equilibrium in accumulated CAM compounds. 0, 0.05, 0.20, and 1.0 micro g/ml hydrocortisone was added to the nutrient media during the entire culture period. Cells were liberated and levels of CAM aggrecan, type II collagen, and fibronectin, of intracellular IGF-1, IL1alpha and beta, and of their respective plasma membrane bound receptors IGFR1, IL1RI, and the decoy receptor IL1RII, were assayed by flow cytometry.
In comparison with controls, hydrocortisone treated chondrocytes, at all concentrations, expressed significantly higher plasma membrane bound IGFR1. Intracellular IGF-1 levels remained unchanged. Together with these changes, reflecting an increased ability to synthesise extracellular matrix (ECM) macromolecules, hydrocortisone treated cells expressed significantly higher amounts of the plasma membrane bound decoy IL1RII. Concurrently, intracellular IL1alpha and beta levels and membrane bound IL1RI were down regulated. Levels of CAM aggrecan, type II collagen, and fibronectin were significantly up regulated in the chondrocytes treated with hydrocortisone.
0.05 micro g/ml hydrocortisone treated chondrocytes had decreased catabolic signalling pathways and showed an enhanced ability to synthesise ECM macromolecules. Because IL1 activity was decreased and the expression of IL1RII decoy receptor enhanced, more of the ECM macromolecules produced remained accumulated in the CAM of the chondrocytes. The effects were obtained at doses comparable with physiological plasma levels of hydrocortisone in humans.
研究生理剂量的氢化可的松对从正常关节软骨获取的人软骨细胞相关基质（CAM）合成及更新的影响。
从五名供体股骨髁表面完整的软骨获取人关节软骨细胞，培养一周以使CAM化合物积累达到平衡。在整个培养期间，向营养培养基中添加0、0.05、0.20和1.0μg/ml的氢化可的松。通过流式细胞术分析细胞释放后CAM聚集蛋白聚糖、II型胶原蛋白、纤连蛋白、细胞内胰岛素样生长因子-1（IGF-1）、白细胞介素1α（IL1α）和白细胞介素1β（IL1β）及其各自质膜结合受体胰岛素样生长因子受体1（IGFR1）、白细胞介素1受体I型（IL1RI）和诱饵受体白细胞介素1受体II型（IL1RII）的水平。
与对照组相比，所有浓度的氢化可的松处理的软骨细胞均表达显著更高的质膜结合IGFR1。细胞内IGF-1水平保持不变。伴随着这些反映合成细胞外基质（ECM）大分子能力增强的变化，氢化可的松处理的细胞表达显著更高量的质膜结合诱饵IL1RII。同时，细胞内IL1α和IL1β水平以及膜结合IL1RI下调。氢化可的松处理的软骨细胞中CAM聚集蛋白聚糖、II型胶原蛋白和纤连蛋白水平显著上调。
0.05μg/ml氢化可的松处理的软骨细胞分解代谢信号通路减少，合成ECM大分子的能力增强。由于IL1活性降低且IL1RII诱饵受体表达增强，产生的更多ECM大分子保留在软骨细胞的CAM中。这些效应在与人类生理血浆水平相当的剂量下即可获得。
