Human knee and ankle cartilage explants: catabolic differences
Human knee and ankle cartilage explants: catabolic differences
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DOI：
10.1016/s0736-0266(01)00125-5
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发表时间：
2002-05-01
影响因子：
2.8
通讯作者：
Cole, AA
中科院分区：
文献类型：
--
作者：
Eger, W;Schumacher, BL;Cole, AA
骨关节炎（OA）的患病率在某些关节中较低，即，脚踝比膝盖更痛我们比较了成人供体（配对）同一肢体的这两个关节的软骨。迄今为止，我们的数据表明，有两个关节软骨之间的代谢，生物化学和生物力学的差异。目前的研究重点是通过分析硫酸盐掺入糖胺聚糖（GAG）作为蛋白聚糖（PG）合成的测量指标，扩展比较软骨细胞对白细胞介素-1 β（IL-1 β）和成骨蛋白I（OP-1）的反应的代谢研究。作为外植体培养的正常膝关节（胫股）和踝关节（距小腿）的成人软骨细胞在72 h后均通过减少PG合成对IL-1 β产生反应;然而，膝关节软骨细胞的IC 50为6.2 pg/ml，而踝关节为35 pg/ml。当外植体与IL-1 β孵育72小时，并允许在没有IL-1 β的情况下反弹时，5天内踝关节软骨细胞的PG合成显著升高：膝关节软骨细胞即使在8天后也无法显著增加合成。然而，在膝关节和踝关节中，OP-1的应用增强了反弹期的PG合成。在对IL-1的反应中，蛋白酶活性的上调可通过在膝关节软骨的深区中由聚集蛋白聚糖酶和基质金属蛋白酶（MMP）蛋白水解产生的新表位的增加来检测。基质溶解素和胶原酶也上调。这些研究的数据证实，去除IL-1后，踝关节对分解代谢刺激的反应较低，对合成代谢刺激的反应更高。两个关节软骨之间代谢活动的差异可能有助于解释它们对OA易感性的差异。(C)2002骨科研究学会。由Elsevier Science Ltd.出版，版权所有。
The prevalence of osteoarthritis (OA) is lower in some joints, i.e., the ankle, than in the knee. We have compared the cartilages from these two joints of the same limb in adult donors (matched pairs). Our data to date suggest that there are metabolic, biochemical and biomechanical differences between the cartilages of the two joints. The current study has focused on extending the metabolic studies comparing the response of chondrocytes to Interleukin-1beta (IL-1beta) and osteogenic protein I (OP-1) by analyzing changes in sulfate incorporation into glycosaminoglycans (GAGs) as a measure of proteoglycan (PG) synthesis. Human adult chondrocytes from normal knees (tibiofemoral) and ankles (talocrural) joints cultured as explants both responded to IL-1beta after 72 h by decreasing PG synthesis; however, the IC50 for the knee chondrocytes was 6.2 pg/ml, while that for the ankle was 35 pg/ml. When the explants were incubated for 72 h with IL-1beta and allowed to rebound without IL-1beta, synthesis of PG was significantly elevated by ankle chondrocytes within five days: knee chondrocytes were unable to significantly increase synthesis even after eight days. However, in both knee and ankle, application of OP-1 enhanced PG synthesis in the rebound phase. In response to IL-1, an upregulation of proteinase activity was detectable by an increase in the neoepitopes proteolytically-generated by both aggrecanase and matrix metalloproteinases (MMPs), in the deep zone of the knee cartilage. Stromelysin and collagenase were upregulated as well. The data emerging from these studies confirm that the ankle is less responsive to catabolic stimulation and more responsive to anabolic stimulation following IL-1 removal. These differences in metabolic activity between the cartilages of the two joints could in part help to explain their differences in susceptibility to OA. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.