Stöve Johannes, Schöniger Ralf, Huch Klaus, Brenner Rolf, Günther Klaus-Peter, Puhl Wolfhart, Scharf Hanns-Peter
Department of Orthopaedic Surgery, University of Heidelberg, Mannheim, Germany.
Acta Orthop Scand. 2002 Oct;73(5):562-7. doi: 10.1080/000164702321022857.
We studied the effects of dexamethasone on proteoglycan (PG) concentration and gene expression in human osteoarthrotic chondrocytes stimulated with IL-1beta. Cartilage samples were taken from 7 patients with osteoarthrosis of the knee and chondrocytes cultivated in alginate beads. Dexamethasone was added in three concentrations (10(-5), 10(-6), 10(-7) M) to IL-1beta (100 pg/nL)-stimulated chondrocytes. PG concentration was estimated by a dimethylmethylene blue assay. To assess cell proliferation, DNA content was measured fluorometrically. Quantitative Lightcycler-PCR was used to estimate the mRNA levels of stromelysin-1 (MMP-3) and aggrecan (AGG). The proliferation rate was unchanged in all treatment groups. IL-1beta increased MMP-3 expression by 44% and inhibited AGG expression by 16%, but PG-concentration was reduced by 7%. The addition of dexamethasone to IL-1beta-stimulated chondrocytes further reduced the PG concentration by 19% at 10(-5) M and by 17% at 10(-7) M. The MMP-3 expression was inhibited between 27-53% and the AGG expression between 30-46% by dexamethasone. In osteoarthrotic chondrocytes, dexamethasone in an appropriate dose range reduced the expression of MMP-3 and AGG at the same time. The resulting decrease in PG concentration should be considered when using intraarticular corticosteroids to treat an osteoarthrotic joint.
我们研究了地塞米松对白细胞介素-1β刺激的人骨关节炎软骨细胞中蛋白聚糖（PG）浓度和基因表达的影响。从7例膝关节骨关节炎患者获取软骨样本，并将软骨细胞培养于藻酸盐珠中。将三种浓度（10⁻⁵、10⁻⁶、10⁻⁷M）的地塞米松添加至白细胞介素-1β（100 pg/nL）刺激的软骨细胞中。通过二甲基亚甲基蓝法测定PG浓度。为评估细胞增殖，采用荧光法测量DNA含量。运用定量Lightcycler-PCR法估算基质金属蛋白酶-1（MMP-3）和聚集蛋白聚糖（AGG）的mRNA水平。所有治疗组的增殖率均未改变。白细胞介素-1β使MMP-3表达增加44%，并使AGG表达抑制16%，但PG浓度降低了7%。在白细胞介素-1β刺激的软骨细胞中添加地塞米松，在10⁻⁵M时使PG浓度进一步降低19%，在10⁻⁷M时降低17%。地塞米松使MMP-3表达抑制27%-53%，使AGG表达抑制30%-46%。在骨关节炎软骨细胞中，适当剂量范围的地塞米松可同时降低MMP-3和AGG的表达。在使用关节内皮质类固醇治疗骨关节炎关节时，应考虑由此导致的PG浓度降低。
