Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes

Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes
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DOI:
10.1016/s0002-9440(10)63024-6
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发表时间:
2001-11-01
影响因子:
6
通讯作者:
Kirsch, T
Kirsch, T
中科院分区:
医学2区
文献类型:
--
作者:
Pfander, D;Swoboda, B;Kirsch, T

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虽然骨关节炎的特征在于细胞外软骨基质的进行性损失,但对疾病进展过程中关节软骨细胞的命运知之甚少。在这项研究中,我们研究了syndecan-3,早期软骨细胞分化的标志物,和膜联蛋白VI,晚期软骨细胞分化的标志物,在哺乳动物胚胎生长板软骨和正常和骨关节炎的人关节软骨的表达。而syndecan-3在生长板软骨的增殖和肥大区中表达,膜联蛋白VI的免疫染色主要发现在胎牛生长板软骨的肥大和矿化区。正常人关节软骨中约20%的软骨细胞对syndecan-3呈免疫阳性,在骨关节炎进展期间,表达syndecan-3的软骨细胞数量显着增加,在严重受累的骨关节炎软骨的上部区域,超过80%的syndecan-3阳性细胞。类似地,在骨关节炎的进展过程中,在上部软骨区中膜联蛋白VI表达细胞的数量显著增加。此外,免疫染色增殖细胞核抗原,细胞增殖的标志物,检测软骨细胞;在骨关节炎软骨的上部区域。使用针对syndecan-3和膜联蛋白VI的抗体进行的双标记实验揭示了软骨细胞;仅表达syndecan-3的细胞,以及同时表达syndecan-3和膜联蛋白VL的细胞。这些结果表明,早期(增殖细胞核抗原,syndecan-3)和晚期分化标记物(膜联蛋白VI,碱性磷酸酶)的表达在骨关节炎软骨的软骨细胞中被激活。
Although osteoarthritis is characterized by a progressive loss of the extracellular cartilage matrix, very little is known about the fate of articular chondrocytes during the progression of the disease. In this study we examined the expression of syndecan-3, a marker of early chondrocyte differentiation, and annexin VI, a marker of late chondrocyte differentiation, in mammalian embryonic growth plate cartilage and normal and osteoarthritic human articular cartilage. Whereas syndecan-3 was expressed in the proliferative and hypertrophic zones of growth plate cartilage, immunostaining for annexin VI was predominately found in the hypertrophic and mineralizing zones of fetal bovine growth plate cartilage. Approximately 20% of chondrocytes were immunopositive for syndecan-3 in normal human articular cartilage, the number of syndecan-3-expressing chondrocytes significantly increased during the progression of osteoarthritis with more than 80% syndecan-3-positive cells in the upper zone of severely affected osteoarthritic cartilage. Similarly, the number of annexin VI-expressing cells significantly increased in the upper cartilage zones during the progression of osteoarthritis. Furthermore, immunostaining for proliferating cell nuclear antigen, a marker for cell proliferation, was detected in chondrocytes; in the upper zone of osteoarthritic cartilage. Double-labeling experiments with antibodies against syndecan-3 and annexin VI revealed chondrocytes; that expressed only syndecan-3, and cells that expressed both syndecan-3 and annexin VL These results suggest that the expression of early (proliferating cell nuclear antigen, syndecan-3) and late differentiation markers (annexin VI, alkaline phosphatase) is activated in chondrocytes of osteoarthritic cartilage.