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首页> 外文期刊>Arthritis research & therapy. >Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-kappaB ligand.
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Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-kappaB ligand.

机译：组织蛋白酶K在人椎间盘中的组成性表达：通过组织蛋白酶K和核因子-κB配体的受体激活剂对椎间盘细胞外基质重塑的新见解。

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INTRODUCTION: Cathepsin K is a recently discovered cysteine protease which cleaves the triple helical domains of type I to II collagen. It has been shown to be up-regulated in synovial tissue from osteoarthritic and rheumatoid patients, and is a component in normal and nonarthritic cartilage, where it increases with aging. Studies on heart valve development have recently shown that receptor activator of nuclear factor-kappaB ligand (RANKL) acts during valve remodeling to promote cathepsin K expression. Since extracellular matrix remodeling is a critical component of disc structure and biomechanical function, we hypothesized that cathepsin K and RANKL may be present in the human intervertebral disc. METHODS: Studies were performed following approval of the authors' Human Subjects Institutional Review Board. Six annulus specimens from healthier Thompson grade I to II discs, and 12 specimens from more degenerate grade III to IV discs were utilized in microarray analysis of RANKL and cathepsin K gene expression. Immunohistochemistry was also performed on 15 additional disc specimens to assess the presence of RANKL and cathepsin K. RESULTS: Cathepsin K gene expression was significantly greater in more degenerated grade III to IV discs compared to healthier grade I to II discs (P = 0.001). RANKL was also identified with immunohistochemistry and molecular analyses. RANKL gene expression was also significantly greater in more degenerated discs compared to healthier ones (P = 0.0001). A significant linear positive correlation was identified between expression of cathepsin K and RANKL (r(2) = 92.2; P < 0.0001). CONCLUSIONS: Extracellular matrix remodeling is a key element of disc biology. Our use of an appropriate antibody and gene expression studies showed that cathepsin K is indeed present in the human intervertebral disc. Immunolocalization and molecular analyses also confirmed that RANKL is present in the human disc. Expression of RANKL was found to be significantly greater in more degenerated compared to healthier discs (P = 0.0001). Cathepsin K gene expression levels showed a positive, significant correlation with RANKL expression. Based on these data, we propose that cathepsin K plays a significant role in disc matrix remodeling and in matrix degradation in the proinflammatory cytokine-rich microenvironment of the degenerating disc.
机译：简介：组织蛋白酶K是最近发现的半胱氨酸蛋白酶，可切割I型至II型胶原的三螺旋结构域。已显示它在骨关节炎和类风湿性关节炎患者的滑膜组织中上调，并且是正常和非关节炎软骨的一个组成部分，随着年龄的增长而增加。心脏瓣膜发育的研究最近表明，核因子-κB配体的受体激活剂（RANKL）在瓣膜重构过程中起促进组织蛋白酶K表达的作用。由于细胞外基质重塑是椎间盘结构和生物力学功能的关键组成部分，我们假设组织蛋白酶K和RANKL可能存在于人类椎间盘中。方法：研究在作者的人类受试者机构审查委员会批准后进行。较健康的Thompson I至II级椎间盘标本有6个瓣环标本，以及更退化的III至IV级椎间盘标本中的12个标本被用于RANKL和组织蛋白酶K基因表达的微阵列分析。还对另外15个椎间盘标本进行了免疫组织化学，以评估RANKL和组织蛋白酶K的存在。结果：与更健康的I至II级椎间盘相比，在更退化的III至IV级椎间盘中组织蛋白酶K基因的表达明显更高（P = 0.001）。还通过免疫组织化学和分子分析鉴定了RANKL。与更健康的椎间盘相比，在退化性更强的椎间盘中，RANKL基因表达也显着更高（P = 0.0001）。组织蛋白酶K和RANKL的表达之间存在显着的线性正相关（r（2）= 92.2; P <0.0001）。结论：细胞外基质重塑是椎间盘生物学的关键因素。我们使用适当的抗体和基因表达研究表明，组织蛋白酶K确实存在于人的椎间盘中。免疫定位和分子分析也证实人盘中存在RANKL。与更健康的椎间盘相比，发现RANKL的表达在更多的变性中明显更高（P = 0.0001）。组织蛋白酶K基因表达水平与RANKL表达呈正相关。基于这些数据，我们建议组织蛋白酶K在变性椎间盘富含促炎细胞因子的微环境中，在椎间盘基质重塑和基质降解中起重要作用。

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