Chen Jinghong, Luo Mingxiu, Wang Wei, Zhang Zentie, He Ying, Duance Victor C, Hughes Clare E, Caterson Bruce, Cao Junling
Institute of Endemic Diseases, Xi'an Jiaotong University College of Medicine, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, Shaanxi, P.R., China.
J Orthop Res. 2015 Jan;33(1):47-55. doi: 10.1002/jor.22708. Epub 2014 Sep 26.
Kashin-Beck disease (KBD) is a chronic, deforming endemic osteoarticular disease with altered metabolism of the cartilage matrix. Matrix metalloproteinases (MMPs), aggrecanases (ATAMTSs), and their inhibitors (TIMPs) play important roles in cartilage formation and matrix degradation. This study investigated these proteases and inhibitors in young KBD cartilage. The percentages of chondrocytes staining for MMP-1/-13 and MMP-generated DIPEN neoepitope, aggrecanase-generated ITEGE neoepitope in aggrecan in KBD patients were significantly higher than in controls. However, TIMP-1 was significantly less numerous than in controls in the superficial and middle zones of KBD samples, the percentage of chondrocytes staining for the TIMP-2 was significantly higher than in controls. Staining for MMP-1/-13 and, TIMP-1/-2 in KBD patients was prominent in the superficial zone and the middle zone of articular cartilage. Staining for ITEGE and DIPEN neoepitopes in KBD samples was prominent in the superficial zone and the middle zone of articular cartilage. The strongest staining for the MMP and aggrecanase-generated neoepitopes was adjacent to areas of chondronecrosis. These results indicated that KBD cartilage destruction depends on collagen- and aggrecan-degrading proteases such as collagenases (MMP-1/-13), as well as aggrecanases. Increased TIMP-2 level adjacent to necrotic areas suggest that attempted repair mechanism are also activated.
大骨节病（KBD）是一种慢性、变形性地方性骨关节病，伴有软骨基质代谢改变。基质金属蛋白酶（MMPs）、聚糖酶（ATAMTSs）及其抑制剂（TIMPs）在软骨形成和基质降解中起重要作用。本研究调查了年轻大骨节病软骨中的这些蛋白酶和抑制剂。大骨节病患者软骨细胞中MMP-1/-13和MMP产生的DIPEN新表位、聚糖酶产生的聚糖ITEGE新表位的染色百分比显著高于对照组。然而，在大骨节病样本的表层和中层区域，TIMP-1的数量明显少于对照组，TIMP-2染色的软骨细胞百分比显著高于对照组。大骨节病患者关节软骨表层和中层区域MMP-1/-13以及TIMP-1/-2的染色明显。大骨节病样本中ITEGE和DIPEN新表位的染色在关节软骨表层和中层区域明显。MMP和聚糖酶产生的新表位染色最强的部位与软骨坏死区域相邻。这些结果表明，大骨节病软骨破坏取决于胶原和聚糖降解蛋白酶，如胶原酶（MMP-1/-13）以及聚糖酶。坏死区域附近TIMP-2水平升高表明修复机制也被激活。
