Effects of lysosomal enzymes on the type of collagen synthesized by bovine articular cartilage.
Effects of lysosomal enzymes on the type of collagen synthesized by bovine articular cartilage.
复制标题
溶酶体酶对牛关节软骨合成胶原类型的影响。
DOI：
10.1016/0006-291x(73)90679-7
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发表时间：
1973
影响因子：
3.1
通讯作者：
M. Nimni
中科院分区：
文献类型：
--
作者：
K. Deshmukh;M. Nimni
牛关节软骨通常合成含有三个相同α链的胶原蛋白。与大鼠肝溶酶体酶预孵育后，开始合成大量更普遍存在的（α1）2α 2型胶原。由于骨关节炎中溶酶体增加，可能是这些酶引起了退行性变区域细胞的异常生物合成模式。关节软骨是一种细胞密度非常低的无血管组织，主要由细胞外物质如胶原、蛋白多糖和糖蛋白组成。该组织的结构完整性取决于这些组分的相对比例、性质和结构组织。直到最近，在骨关节炎中看到的软骨破坏被认为是由“磨损”过程引起的。这一概念没有得到最近的超微结构和生化研究结果的证实。受累区域的细胞活性导致软骨细胞克隆扩大，细胞内细胞器数量增加，反映了合成和分泌活性（1）。退行性病变的严重程度与组织中的糖胺聚糖含量呈负相关（2-7）。另一方面，骨关节炎中放射性硫酸盐掺入增加，这表明参与修复病变的细胞试图修复病变（2）。在这些条件下合成的蛋白聚糖的性质（硫酸角质素较少，4-硫酸软骨素较多）反映了未成熟成软骨细胞的行为（3-8）。溶酶体蛋白酶与基质降解相关（9-12）。在早期骨关节炎病变中，分别在pH 5.0和7.0下降解蛋白聚糖的组织蛋白酶-D和中性蛋白酶显著增加（13-15）。虽然骨关节炎中软骨的胶原含量没有变化，但可能存在质的差异。最近，我们发现正常人软骨仅合成软骨型胶原或（α1-II型）3，而骨关节炎软骨还合成大量的（α1）2α 2胶原（皮肤型）（16）。关节软骨胶原蛋白与其他普遍存在的哺乳动物胶原蛋白形式完全不同。除了含有三条相同的α链外，它还含有比其他组织胶原蛋白多四至五倍的羟基赖氨酸和糖苷结合碳水化合物（17）。很有可能的是，细胞在退化部位沉积的异常胶原蛋白可能导致机械结构变弱，并导致软骨损失。在试图阐明这种异常代谢模式的机制时，很明显溶酶体酶可以改变正常软骨细胞的功能，使它们合成非特异性胶原蛋白分子。
Bovine articular cartilage normally synthesizes a collagen containing three identical α-chains. After pre-incubation with rat liver lysosomal enzymes, it begins to synthesize significant amounts of the more ubiquitous collagen of the (α1)2α2type. Since lysosomes are increased in osteoarthritis, it is possible that the abnormal biosynthetic patterns exhibited by cells in areas of degeneration are caused by such enzymes.Articular cartilage is an avascular tissue with very low cell density, composed primarily of extracellular substances such as collagen, proteoglycans, and glycoproteins. The structural integrity of this tissue depends on the relative proportion, nature, and structural organization of these components. Until recently, the destruction of cartilage seen in osteoarthritis was considered to result from a “wear and tear” process. This concept is not substantiated by recent ultrastructural and biochemical findings. Cellular activity in the involved areas leads to enlarged clones of chondrocytes containing increased numbers of intracellular organelles reflecting synthetic and secretory activity (1). There is an inverse correlation between the severity of the degenerative changes and the glycosaminoglycan content of the tissue (2–7). On the other hand, radioactive sulfate incorporation increases in osteoarthritis, an indication of the attempts made by the cells involved to repair the lesion (2). The nature of the proteoglycans synthesized under these conditions (less keratan sulfate and more chondroitin-4-sulfate) reflect the behaviour of immature chondroblasts (3–8). Lysosomal proteases have been associated with the degradation of the matrix (9–12). Cathepsin-D and a neutral protease which degrade proteoglycans at pH 5.0 and 7.0 respectively are considerably increased in early osteoarthritic lesions (13–15). Although the collagen content of cartilage does not change in osteoarthritis, qualitative differences may exist. Recently, we have shown that whereas normal human cartilage synthesizes only cartilage type collagen or (α1-Type II)3, osteoarthritic cartilage synthesizes in addition significant amounts of (α1)2α2collagen (skin type) (16). Articular cartilage collagen is quite different from other ubiquitous forms of mammalian collagens. In addition to containing three identical α-chains, it has four to five times more hydroxylysine and glycosidically associated carbohydrate than collagen from other tissues (17). It is quite possible that the abnormal collagen deposited by the cells at the site of degeneration may give rise to a mechanically weaker structure and lead to a loss of cartilage. While attempting to elucidate the mechanism underlying this abnormal metabolic pattern, it became apparent that lysosomal enzymes can alter the function of normal cartilage cells causing them to synthesize non-specific collagen molecules.