Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage.
Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage.
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DOI：
10.1186/ar3839
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发表时间：
2012-05-14
影响因子：
4.9
通讯作者：
Poole AR
中科院分区：
文献类型：
--
作者：
Dejica VM;Mort JS;Laverty S;Antoniou J;Zukor DJ;Tanzer M;Poole AR
通过免疫化学方法检测，随着年龄的增长和软骨骨关节炎(OA)的发生，包括胶原酶和组织蛋白酶K在内的蛋白水解酶对II型胶原的螺旋内裂解增加。对正常人和骨性关节炎患者股骨髁部软骨中胶原酶和组织蛋白酶K产生的胶原裂解部位进行了鉴定和比较。固定的冰冻软骨切片用与胶原酶产生的裂解新表位C2C和C1.2C反应的抗体和II型胶原产生的初级裂解新表位(C2K)的抗体进行免疫组织化学检测，这些表位是通过组织蛋白酶K的作用和可能由其他酶产生的，但不是通过迄今研究的任何胶原酶。在大多数情况下，所有三个表位的胶原裂解染色模式都是相似的：在年轻个体的非骨关节炎软骨中主要是细胞周围的弱到中度染色，而在老化和骨关节炎软骨中的染色更强、更广泛，通常从组织的浅层延伸到中/深层。在非常退化的骨性关节炎标本中，关节表面明显破坏，染色分布在大部分软骨基质中。蛋白水解酶对胶原的裂解通常发生在关节表面及其附近的软骨细胞周围，随后变得更加强烈，随着年龄的增长和骨关节炎逐渐深入到软骨中。这些产物的分布之间的密切对应关系表明，胶原酶和组织蛋白酶K以及其他可能产生这个独特的组织蛋白酶K裂解位点的蛋白酶通常在同一位置上活跃于降解II型胶原的过程中。
The intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared. Fixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date. In most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix. Cleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.
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影响因子：
5
作者：
Goldring, M B
通讯作者：
Goldring, M B
影响因子：
7
作者：
DeGroot, J;Verzijl, N;Lafeber, FPJG
通讯作者：
Lafeber, FPJG
影响因子：
15.9
作者：
AIGNER, T;BERTLING, W;VONDERMARK, K
通讯作者：
VONDERMARK, K
影响因子：
7
作者：
Connor, J. R.;LePage, C.;Kumar, S.
通讯作者：
Kumar, S.
影响因子：
--
作者：
Lohmander, LS;Atley, LM;Eyre, DR
通讯作者：
Eyre, DR