摘要
目的检测组织蛋白酶K( Cathepsin-k)在人膝关节骨关节炎软骨标本和正常人膝关节软骨标本中的表达和分布,探讨组织蛋白酶k表达与骨性关节炎软骨退变之间的关系。
方法收集正常人膝关节软骨标本和早期及中晚期骨关节炎膝关节软骨标本。免疫组化方法及逆转录PCR方法检测组织蛋白酶k在人膝关节骨关节炎软骨标本和正常人膝关节软骨标本中的表达和分布。
结果组织蛋白酶k在骨关节炎软骨基质破坏区域周围软骨细胞中的表达明显增高,特别是在骨关节炎软骨退变早期,在软骨基质最先发生破坏的区域(软骨表层和巢聚软骨细胞周围基质)的软骨细胞中组织蛋白酶K表达明显升高,而在正常软骨软骨细胞仅有少量表达。早期及中晚期骨关节炎组软骨中组织蛋白酶k的表达较正常组明显升高,差异具有显著性意义(P﹤0.05);在组织蛋白酶k mRNA表达水平上,中晚期组较早期组有明显增高,差异具有显著性意义(P﹤0.05)。
结论组织蛋白酶k在骨关节炎软骨基质破坏区域周围软骨细胞中表达明显增高,特别是软骨退变早期在软骨表层软骨细胞和巢聚软骨细胞中的升高表达提示组织蛋白酶k与骨关节炎软骨退变关系密切,特别在早期发病中有重要作用。为骨关节炎的防治提供新的线索。
Objective to observe the distribution and expression of Cathepsin-k in human normal articular cartilage and osteoarthritic articular cartilage and to explore the relation between the Cathepsin-k expression and the pathogenesis of osteoarthritis.
Methods to collect human normal articular cartilage and osteoarthritic articular cartilage in the knee joints and RT-PCR was used to measure mRNA levels of cathepsin K in total RNA extracted from normal cartilage and osteoarthritic cartilage in the knee joints. Immunohistochemistry was used to study the distribution and expression of Cathepsin-k in normal cartilage and osteoarthritic cartilage in the knee joints.
Results Increased expression of Cathepsin-k was found near sites of matrix destruction in articular chondrocytes, particularly in clusters of proliferating cells, At the onset of cartilage degeneration, Obvious increased expression of cathepsin K was found in the vicinity of articular cartilage defects in early osteoarthritic lesions (the surface layer of articular cartilage and the vicinity of clusters of proliferating cells), Cathepsin-k was only seen in a small number of chondrocytes in normal cartilage. The expression of Cathepsin-k in osteoarthritis were obviously higher than those in normal cartilage (P<0.05)and the expression of Cathepsin-k in advanced group were obviously higher than those in mild group at the mRNA level(P<0.05).
Conclusion the up regulation and temporospatial distribution of Cathepsin-k in osteoarthritis cartilage suggests a role for this enzyme in the pathogenesis of osteoarthritis,especially at the onset, Cathepsin-k is closely involved in cartilage degenevation is primarily from the increase of Cathepsin-k. These data may provide new clues for the development of treatments aimed at preventing cartilage degeneration.
引文
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