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首页> 外文期刊>Osteoarthritis and cartilage >Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro.
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Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro.

机译：正常和骨关节炎人关节软骨软骨细胞的细胞外基质的体内稳态。

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OBJECTIVE: In normal articular cartilage cells, the IGFRI/insulin-like growth factor 1 (IGF-1) autocrine pathway was shown to overrule the catabolic effects of the IL-1/IL-1RI pathway by up-regulation of the IL-1RII decoy receptor. The activity of the IGF-1/IGFR1 and IL-1/IL-1R pathways, and of the IL-1RII control mechanism in the synthesis and turnover of the extracellular matrix (ECM) by chondrocytes from normal and osteoarthritic (OA) articular cartilage was compared in order to identify possible therapeutic targets of this disease. METHODS: Phenotypically stable human articular cartilage cells were obtained from normal and OA cartilage of the same knee showing focal OA. The cells were cultured in alginate beads over 1 week to re-establish the intracellular cytokine and growth factors, to reexpress the respective plasma membrane receptors and to reach equilibrium in accumulated cell-associated matrix (CAM) compounds. Following liberation of the cells from the alginate beads, the levels of cell-associated matrix (CAM) aggrecan, type II collagen and fibronectin, of intracellular IGF-1, IL-1alpha and beta and of their respective plasma membrane-bound receptors, IGFR1, IL-1RI and the decoy receptor IL-1RII, were assayed using flow cytometry. RESULTS: Coordinated production and accumulation of CAM aggrecan and type II collagen under the effect of the IGFR1/IGF-1 autocrine pathway-as documented for chondrocytes from healthy controls-was absent when the chondrocytes had been obtained from OA joints. When compared with cells obtained from normal tissues, chondrocytes from fibrillated OA cartilage expressed significantly higher intracellular IGF-1 levels and plasma membrane-bound IGFR1. At the same time, significantly higher intracellular IL-1alpha and beta levels and upregulated plasma membrane-bound IL-1RI were observed. Plasma membrane-bound IL-1RII decoy receptor was downregulated in OA chondrocytes. The levels of CAM aggrecan, type II collagen and fibronectin were significantly reduced in the chondrocytes obtained from pathological tissue. CONCLUSION: Paired analysis of normal and OA chondrocytes from the same knee joint has shown an enhanced capacity of chondrocytes from OA cartilage to produce ECM macromolecules. However, the same cells have increased catabolic signalling pathways. As a consequence of this increased IL-1 activity and the reduced amounts of IL-1RII decoy receptor, less of the produced ECM macromolecules may persist in the CAM of the OA chondrocytes.
机译：目的：在正常的关节软骨细胞中，IGFRI /胰岛素样生长因子1（IGF-1）自分泌途径被证明可以通过上调IL-1RII来抵消IL-1 / IL-1RI途径的分解代谢作用。诱饵受体。 IGF-1 / IGFR1和IL-1 / IL-1R途径的活性以及IL-1RII控制机制在正常和骨关节炎（OA）软骨细胞的软骨细胞合成和转换细胞外基质（ECM）中的作用为了确定该疾病可能的治疗靶点，进行了比较。方法：从表现出局灶性OA的同一膝关节的正常和OA软骨中获得表型稳定的人关节软骨细胞。将细胞在藻酸盐珠中培养1周以上，以重新建立细胞内细胞因子和生长因子，以重新表达各自的质膜受体，并在累积的细胞相关基质（CAM）化合物中达到平衡。从藻酸盐珠释放​​细胞后，细胞相关基质（CAM）聚集蛋白聚糖，II型胶原和纤连蛋白，细胞内IGF-1，IL-1alpha和β以及它们各自的质膜结合受体IGFR1的水平使用流式细胞术测定IL-1RI和诱饵受体IL-1RII。结果：当从OA关节获得软骨细胞时，在IGFR1 / IGF-1自分泌途径的作用下（如来自健康对照组的软骨细胞所证明的），CAM聚集蛋白聚糖和II型胶原的协调生产和积累就不存在了。与从正常组织获得的细胞相比，来自原纤维化OA软骨的软骨细胞表达的细胞内IGF-1水平和血浆膜结合IGFR1明显更高。同时，观察到明显更高的细胞内IL-1α和β水平以及质膜结合的IL-1RI上调。 OA软骨细胞中质膜结合的IL-1RII诱饵受体被下调。从病理组织获得的软骨细胞中，CAM聚集蛋白聚糖，II型胶原和纤连蛋白的水平显着降低。结论：对来自同一膝关节的正常和OA软骨细胞进行配对分析表明，来自OA软骨的软骨细胞产生ECM大分子的能力增强。但是，相同的细胞具有增加的分解代谢信号通路。由于这种增加的IL-1活性和减少的IL-1RII诱饵受体数量，导致更少的产生的ECM大分子可以持续存在于OA软骨细胞的CAM中。

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