Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13.

Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13.
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人类关节软骨细胞产生IL-7并对IL-7作出反应,而基质金属蛋白酶13的产生增加。

DOI:
10.1186/ar2376
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发表时间:
2008
影响因子:
4.9
通讯作者:
Loeser, Richard F.
Loeser, Richard F.
中科院分区:
医学2区
文献类型:
--
作者:
Long, David;Blake, Simon;Song, Xiao-Yu;Lark, Michael;Loeser, Richard F.

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在骨关节炎和类风湿性关节炎患者的关节软骨和滑液中发现了纤连蛋白片段。这些基质碎片可以刺激多种基质破坏介质的产生,包括各种细胞因子和金属蛋白酶。本研究的目的是发现使用纤连蛋白片段作为刺激物的软骨破坏的新介质。人类关节软骨是从组织捐献者和膝​​关节置换手术时取出的骨关节炎软骨中获得的。使用 110 kDa α5β1 整合素结合纤连蛋白片段或 IL-1、IL-6 或 IL-7 过夜刺激无血清培养物中酶促分离的软骨细胞。使用抗体阵列检测释放到介质中的细胞因子和基质金属蛋白酶,并通过 ELISA 进行定量。通过流式细胞术、免疫细胞化学染色和PCR评估IL-7受体表达。发现IL-7是由用纤连蛋白片段处理的软骨细胞产生的。与从正常年轻人关节软骨中分离的细胞相比,从老年组织供体和骨关节炎软骨中分离的细胞中发现 IL-7 的产生增加。与分解代谢细胞因子 IL-1 和 IL-6 联合治疗也刺激了软骨细胞 IL-7 的产生。研究发现软骨细胞表达 IL-7 受体,并对 IL-7 刺激做出反应,增加基质金属蛋白酶 13 的产生,并从软骨外植体中释放蛋白聚糖。这些新发现表明,IL-7 可能会导致骨关节炎等关节疾病中的软骨破坏。
Fibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis. These matrix fragments can stimulate production of multiple mediators of matrix destruction, including various cytokines and metalloproteinases. The purpose of this study was to discover novel mediators of cartilage destruction using fibronectin fragments as a stimulus. Human articular cartilage was obtained from tissue donors and from osteoarthritic cartilage removed at the time of knee replacement surgery. Enzymatically isolated chondrocytes in serum-free cultures were stimulated overnight with the 110 kDa α5β1 integrin-binding fibronectin fragment or with IL-1, IL-6, or IL-7. Cytokines and matrix metalloproteinases released into the media were detected using antibody arrays and quantified by ELISA. IL-7 receptor expression was evaluated by flow cytometry, immunocytochemical staining, and PCR. IL-7 was found to be produced by chondrocytes treated with fibronectin fragments. Compared with cells isolated from normal young adult human articular cartilage, increased IL-7 production was noted in cells isolated from older adult tissue donors and from osteoarthritic cartilage. Chondrocyte IL-7 production was also stimulated by combined treatment with the catabolic cytokines IL-1 and IL-6. Chondrocytes were found to express IL-7 receptors and to respond to IL-7 stimulation with increased production of matrix metalloproteinase-13 and with proteoglycan release from cartilage explants. These novel findings indicate that IL-7 may contribute to cartilage destruction in joint diseases, including osteoarthritis.
DOI: 10.1007/s11926-000-0021-y
发表时间: 2000-12-01
影响因子: 5
作者:
Goldring, M B
通讯作者: Goldring, M B
DOI: 10.1053/joca.1998.0116
发表时间: 1998-07-01
影响因子: 7
作者:
Homandberg, GA;Wen, C;Hui, F
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发表时间: 2003-02-01
影响因子: 27.4
作者:
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通讯作者: Lafeber, FPJG
DOI: 10.1042/bj3210751
发表时间: 1997-02-01
影响因子: 4.1
作者:
Homandberg, GA;Hui, F;Harris, A
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