Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes
Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes
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DOI：
10.1002/path.2313
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发表时间：
2008-03-01
影响因子：
7.3
通讯作者：
Alcaraz, M. J.
中科院分区：
文献类型：
--
作者：
Guillen, M. I.;Megias, J.;Alcaraz, M. J.
促炎细胞因子、基质金属蛋白酶（MMPs）和其他分解代谢因子参与骨关节炎（OA）软骨损伤的发病机制。促炎细胞因子如白细胞介素-1 β（IL-1 β）介导软骨降解，可能参与OA的进展。以前，我们发现血红素加氧酶-1（HO-1）在OA软骨细胞中被促炎细胞因子下调，而被IL-10上调。本研究的目的是确定HO-1是否可以改变OA软骨和软骨细胞中IL-1 β的分解代谢作用。通过放射性测量程序、免疫印迹和免疫细胞化学确定，钴原卟啉IX上调HO-1显着减少了OA软骨外植体中IL-1 β引起的糖胺聚糖降解，但增加了原代培养中OA软骨细胞中糖胺聚糖合成和II型胶原的表达。HO-1降低细胞外信号调节激酶1/2的活化。这伴随着MMP活性和胶原酶MMP-1和MMP-13在蛋白和mRNA水平上的表达的显著抑制。此外，HO-1诱导导致胰岛素样生长因子-1的产生显著增加，胰岛素样生长因子结合蛋白-3的水平降低。我们已经在OA患者软骨细胞和关节外植体的原代培养中显示HO-1抵消IL-1 β的分解代谢和抗合成代谢作用。因此，我们的数据表明，HO-1可能是一个调节OA细胞外基质成分的降解和合成的因素。版权所有（c）2008大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and other catabolic factors participate in the pathogenesis of cartilage damage in osteoarthritis (OA). Pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta) mediate cartilage degradation and might be involved in the progression of OA. Previously, we found that haem oxygenase-1 (HO-1) is down-regulated by pro-inflammatory cytokines and up-regulated by IL-10 in OA chondrocytes. The aim of this study was to determine whether HO-1 can modify the catabolic effects of IL-1 beta in OA cartilage and chondrocytes. Up-regulation of HO-1 by cobalt protoporphyrin IX significantly reduced glycosaminoglycan degradation elicited by IL-1 beta in OA cartilage explants but increased glycosaminoglycan synthesis and the expression of collagen II in OA chondrocytes in primary culture, as determined by radiometric procedures, immunoblotting and immunocytochemistry. HO-1 decreased the activation of extracellular signal-regulated kinase 1/2. This was accompanied by a significant inhibition in MMP activity and expression of collagenases MMP-1 and MMP-13 at the protein and mRNA levels. In addition, HO-1 induction caused a significant increase in the production of insulin-like growth factor-1 and a reduction in the levels of insulin-like growth factor binding protein-3. We have shown in primary culture of chondrocytes and articular explants from OA patients that HO-1 counteracts the catabolic and anti-anabolic effects of IL-1 beta. Our data thus suggest that HO-1 may be a factor regulating the degradation and synthesis of extracellular matrix components in OA. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.