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首页> 外文期刊>Spine >Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells.
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Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells.

机译：大鼠椎间盘细胞中胰岛素样生长因子-I依赖蛋白聚糖合成的年龄相关性下降的机制。

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STUDY DESIGN: Age-related fluctuations in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells were investigated. OBJECTIVES: The purpose of this study was to determine whether synthetic responses to insulin-like growth factor-I decline with age and to explore the possibility that an age-related increase in the expression of insulin-like growth factor binding proteins suppresses matrix synthesis in intervertebral disc cells. SUMMARY AND BACKGROUND DATA: Several studies have reported that the responsiveness of chondrocytes to insulin-like growth factor-I decreases with age and furthermore that this phenomenon may be related to increased expression of insulin-like growth factor binding proteins by chondrocytes. MATERIALS AND METHODS: Nucleus pulposus tissue and cells were obtained from the coccygeal vertebrae of 8-week-old, 40-week-old, and 120-week-old rats. Age-related changes in the expression of insulin-like growth factor-I and its receptor were assessed together with insulin-like growth factor-I dependent proteoglycan synthesis by the cultured nucleus pulposus cells. Also, western blot analysis of insulin-like growth factor binding protein-1 was carried out, and further examination was performed of insulin-like growth factor-I signal transduction through tyrosine phosphorylation of insulin receptor substrate-1, which is a signal transducer of insulin-like growth factor-I. RESULTS: Semiquantitative reverse transcription polymerase chain reaction analysis indicated that the expression of insulin-like growth factor-I receptor in 120-week cells decreased clearly in comparison with the cells of younger animals. By contrast, insulin-like growth factor-I dependent proteoglycan synthesis decreased with age, and the sharpest decline of synthesis was found between 8-week and 40-week cells, although the level of insulin-like growth factor-I/insulin-like growth factor-I receptor gene expression was maintained in 40-week-old animals. Consistent with the results of proteoglycan synthesis, the expression of phosphorylated insulin receptor substrate-1 decreased with age. Thus, the expression of insulin-like growth factor binding protein-1 and proteoglycan synthesis was investigated by use of Long R3 insulin-like growth factor-I, which was not influenced by insulin-like growth factor binding proteins. Insulin-like growth factor binding protein-1 was strongly expressed in 40-week cells in comparison with the expression in 8-week cells. Furthermore, proteoglycan synthesis in 40-week cells supplemented with Long R3 insulin-like growth factor-I was upregulated in comparison with that in 40-week cells supplemented with insulin-like growth factor-I. CONCLUSION: The present findings indicate that the age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in nucleus pulposus is caused, at least in part, by the increase in insulin-like growth factor binding proteins at the early stages of aging, and further suggest that a loss of proteoglycan synthesis during the late stages of aging is caused by the downregulation of insulin-like growth factor-I receptor in addition to an increase in insulin-like growth factor binding proteins.
机译：研究设计：研究了大鼠椎间盘细胞中胰岛素样生长因子-I依赖性蛋白聚糖合成的年龄相关波动。目的：本研究的目的是确定对胰岛素样生长因子-I的合成反应是否随着年龄的增长而下降，并探讨与年龄相关的胰岛素样生长因子结合蛋白表达的增加抑制基质合成的可能性。椎间盘细胞。概述和背景数据：几项研究报告说，软骨细胞对胰岛素样生长因子-I的反应性随年龄而降低，此外，这种现象可能与软骨细胞胰岛素样生长因子结合蛋白的表达增加有关。材料与方法：髓核组织和细胞取自8周龄，40周龄和120周龄大鼠的尾椎椎骨。通过培养的髓核细胞，评估了胰岛素样生长因子-I及其受体表达的年龄相关变化以及胰岛素样生长因子-I依赖性蛋白聚糖的合成。此外，还进行了胰岛素样生长因子结合蛋白-1的蛋白质印迹分析，并通过胰岛素受体底物1的酪氨酸磷酸化对胰岛素样生长因子-I信号转导进行了进一步检查，这是胰岛素受体底物1的信号转导子。胰岛素样生长因子-I。结果：半定量逆转录聚合酶链反应分析表明，与年轻动物相比，120周细胞中胰岛素样生长因子-I受体的表达明显降低。相比之下，胰岛素样生长因子-I依赖性蛋白聚糖的合成随年龄的增长而下降，尽管胰岛素样生长因子-I /胰岛素样蛋白的水平在8周至40周的细胞中发现最急剧的下降在40周龄的动物中维持了生长因子-1受体基因的表达。与蛋白聚糖合成的结果一致，磷酸化胰岛素受体底物1的表达随年龄下降。因此，通过使用Long R3胰岛素样生长因子-I研究了胰岛素样生长因子结合蛋白-1的表达和蛋白聚糖合成，其不受胰岛素样生长因子结合蛋白的影响。与8周细胞中的表达相比，胰岛素样生长因子结合蛋白-1在40周细胞中强烈表达。此外，与补充有胰岛素样生长因子-I的40周细胞相比，补充有Long R3胰岛素样生长因子-I的40周细胞的蛋白聚糖合成被上调。结论：本研究结果表明，髓核中胰岛素样生长因子-I依赖性蛋白聚糖合成的年龄相关性下降至少部分是由于早期胰岛素样生长因子结合蛋白的增加所致。衰老，并且进一步表明，在衰老的后期蛋白聚糖合成的损失是由胰岛素样生长因子-1受体的下调以及胰岛素样生长因子结合蛋白的增加引起的。

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