Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage
Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage
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DOI：
10.1053/joca.1999.0304
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发表时间：
2000-07-01
影响因子：
7
通讯作者：
Nah, HD
中科院分区：
文献类型：
--
作者：
Kirsch, T;Swoboda, B;Nah, HD
目的：验证人骨关节炎软骨中软骨细胞终末分化可能导致修复机制失效，导致关节软骨结构和功能进行性丧失的假说。设计：采用免疫组化方法对股骨内外侧髁正常膝关节软骨和骨关节炎膝关节软骨进行碱性磷酸酶、膜联蛋白II、膜联蛋白V、X型胶原等终末分化软骨细胞标志物的检测。采用TUNEL标记法检测细胞凋亡。用茜素红S染色和电镜分析检测矿化和基质囊泡。结果：早期和晚期人骨关节炎软骨上带软骨细胞表达碱性磷酸酶、膜联蛋白II、膜联蛋白V和X型胶原。然而，这些通常在肥大和钙化生长板软骨中表达的蛋白，在健康人关节软骨的上、中、深区均未检测到。正常和患骨关节炎的人软骨切片的TUNEL标记表明，晚期骨关节炎软骨上带的软骨细胞发生凋亡改变。此外，在晚期骨关节炎软骨的上区发现了矿物质沉积。针状矿物晶体通常与这些区域的基质囊泡有关，如在钙化生长板软骨中所见。结论：关节间隙附近的骨关节炎软骨细胞发生终末分化，释放含碱性磷酸酶-、膜联蛋白II-和膜联蛋白v的基质囊泡，引发矿物质形成，最终凋亡死亡。因此，这些细胞恢复了类似于生长板软骨软骨细胞终末分化的表型变化，最终导致骨关节炎中关节软骨的破坏。(C) 2000国际骨关节炎研究学会。
Objective: To test the hypothesis that terminal differentiation of chondrocytes in human osteoarthritic cartilage might lead to the failure of repair mechanisms and might cause progressive loss of structure and function of articular cartilage.Design: Markers for terminally differentiated chondrocytes, such as alkaline phosphatase, annexin II, annexin V and type X collagen, were detected by immunohistochemical analysis of human normal and osteoarthritic knee cartilage from medial and lateral femoral condyles. Apoptosis in these specimens was detected using the TUNEL labeling. Mineralization and matrix vesicles were detected by alizarin red S staining and electron microscopic analysis.Results: Alkaline phosphatase, annexin II, annexin V and type X collagen were expressed by chondrocytes in the upper zone of early stage and late stage human osteoarthritic cartilage. However, these proteins, which are typically expressed in hypertrophic and calcifying growth plate cartilage, were not detectable in the upper, middle and deep zones of healthy human articular cartilage. TUNEL labeling of normal and osteoarthritic human cartilage sections provided evidence that chondrocytes in the upper zone of late stage osteoarthritic cartilage undergo apoptotic changes. In addition, mineral deposits were detected in the upper zone of late stage osteoarthritic cartilage. Needle-like mineral crystals were often associated with matrix vesicles in these areas, as seen in calcifying growth plate cartilage.Conclusion: Human osteoarthritic chondrocytes adjacent to the joint space undergo terminal differentiation, release alkaline phosphatase-, annexin II- and annexin V-containing matrix vesicles, which initiate mineral formation, and eventually die by apoptosis. Thus, these cells resume phenotypic changes similar to terminal differentiation of chondrocytes in growth plate cartilage culminating in the destruction of articular cartilage in osteoarthritis. (C) 2000 OsteoArthritis Research Society International.