Effects of tribological stimulation on chondrocyte metabolism and development of functional cartilage tissue structure for joint lubrication

关节软骨是一种独特而有趣的软组织，它覆盖在关节关节的关节表面，起着“承托”的作用，实现关节的平稳运动。然而，支配软骨表面复杂摩擦学功能建立过程的详细机制尚不清楚。本研究项目的目的是通过软骨细胞对关节运动过程中所经历的机械负荷的代谢反应来研究关节润滑的功能性软骨组织结构的发展过程。众所周知，嵌入软骨组织的软骨细胞可以感知施加在组织上的机械应力和应变。软骨细胞随后通过机械转导途径调节其代谢，维持软骨组织结构的功能。在本研究中，我们开发了一种滚动滑动摩擦加载机，它可以实验再现关节关节过程中软骨表面受摩擦力作用的压缩应变、剪切应变和流体剪切等摩擦学刺激。将加载机安装在CO_2培养箱中，对琼脂糖凝胶中三维培养的软骨细胞进行摩擦刺激，考察了摩擦刺激对软骨细胞合成细胞外基质和组织结构发育的影响。软骨细胞琼脂糖标本首先在静态条件下培养3天。然后，在2小时内用Pyrex玻璃滚轮对试样表面进行纯滑动，每天2次，连续5天。结果表明，施用纯滑动剂可增加释放到培养基中的糖胺聚糖（GAG）的量。此外，在加载试件的最上部区域积累了大量的GAG。这些结果可能表明，纯滑动载荷上调了培养标本最上层区域细胞外基质的生物合成，并可能使天然关节软骨表面区域内发现的富含蛋白聚糖的层精细化，并在关节润滑中发挥重要作用。此外，通过实验评估培养软骨细胞-琼脂糖标本内的物质运输特性，了解支架材料对培养软骨细胞营养供应和细胞外基质分子在标本内扩散的影响。在摩擦试验中还检测了蛋白质分子的润滑能力，以估计天然软骨组织和再生软骨组织的边界润滑机制。少

Articular cartilage is one of the unique and interesting soft tissues since it covers articulating surfaces of diarthrodial joints and plays an important role as "bearing" to achieve smooth joint movements. However, the detailed mechanism which governs the establishing process of the sophisticated tribological functions on the cartilage surface has not been clarified yet The purpose of this research project has been to investigate the developing process of functional cartilage tissue structure for the joint lubrication by the metabolic response of chondrocytes to the mechanical loadings experienced during the joint movement.It is well recognized that chondrocytes embedded in cartilage tissue can sense the mechanical stress and strain applied to the tissue. The chondrocytes subsequently regulate their metabolism through the mechanotransduction pathways and maintain the functional cartilage tissue structure. In this study, we have developed a rolling-sliding friction loading machine whic … More h can experimentally reproduce tribological stimulations, such as compressive strain, shear strain and fluid shear, exerted on the cartilage surface by frictional force during joint articulation. The loading machine was installed in CO_2 incubator and used to apply the tribological stimulation to chondrocytes being cultured three dimensionally within agarose gel Then, the effects of the tribological stimulations on the biosynthesis of extracellular matrix by chondrocytes and development of tissue structure were examined.Chondrocytes-agarose specimens were first culture under static condition for three days. Then, pure sliding was applied to the specimen surfaces by Pyrex glass rollers during 2 hours, twice a day for 5 days. Results indicated that the amount of glycosaminoglycan (GAG) released to the culture medium was increased by applying the pure sliding. Moreover, significant amount of GAG was accumulated within the uppermost region of the loaded specimens. These results might be indicating that the loading of pure sliding up-regulated the biosynthesis of extracellular matrix within the uppermost region of cultured specimens and might elaborate the proteoglycan-rich layer which had been identified within the surface region of natural articular cartilage and would be playing the important role in the joint lubrication. In addition, characteristics of the material transport within the cultured chondrocytes-agarose specimen was evaluated experimentally to understand the effect of scaffold materials on the nutrient supply to cultured chondrocytes and the diffusion of extracellular matrix molecules within the specimens. The lubrication ability of protein molecules was also examined in the friction test to estimate the boundary lubrication mechanism of natural and re-generated cartilage tissue. Less