Gene expression in the process of the regeneration of articular cartilage defect-Comparison with the growth process of the articular joint

关节软骨缺损再生过程中的基因表达——与关节生长过程的比较

• 批准号: 12671416
• 负责人: KAWASAKI Kenzo
• 金额: $ 2.11万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671416/
• 关键词: rabbit; articular cartilage; synovial tissue; chondroitin sulfate; chondroitin 6-sulfotransferase; chondroitin 4-sulfotransferase; growth process; knee joint

We aimed to understand the regenerative process of the articular cartilage and by comparing with the process of the maturation of the articular cartilage at the aspect of the gene expression. As the result, chondroitin 6-sulfotransferase enzyme took part in the change in the growth process of the amount of articular cartilage, that is, maturities of the articular cartilage, and it was found that this enzyme was chiefly produced from the synovial tissue. Moreover, chondroitin 4-sulfotransferase enzyme took part in the early stage of the growth process of articular cartilage, which recruiting the cells and proliferating the chondrocytes. Expression of C6ST was correlated with the ratio of CS isomers in articular cartilage. Therefore C6ST may play important roles in maintaining or improving the quality of CS in articular cartilage. To compare adult and fetal repair potentials of the articular cartilage, we also investigated the early process after creating superficial defects in the femoral knee cartilage using rat models. In fetuses of 19th days of gestation, both chondrocytes and the extracellular matrix responded remarkably to the superficial defects in 48 hours after the injury. Staining patterns with safranin O revealed that some components of the extracellular matrix around the wound were modified from 1 hour after injury, and the change spread from the limited region to the entire knee cartilage in 24 hours. The chondrocytes in the area surrounding the wound transiently expressed increased level of c-fos from 1 to 6 hours. The wound remained 1 day after birth, I.e. 72 hours after injury, but was completely repaired 10 days after birth. In contrast, neither visible responses nor transient c-fos expression was observed in 12-weeks-old adult articular cartilage in 48 hours after injury.

我们的目的是了解关节软骨的再生过程，并在基因表达方面与关节软骨的成熟过程进行比较。结果表明，软骨素6-磺酸转移酶参与了关节软骨量的生长过程，即关节软骨的成熟度的变化，并发现该酶主要由滑膜组织产生。此外，软骨素4-磺基转移酶参与了关节软骨生长的早期阶段，募集细胞，促进软骨细胞的增殖。C6ST的表达与关节软骨中CS异构体的比例有关。因此，C6ST在维持或改善关节软骨CS质量方面可能起重要作用。为了比较成人和胎儿关节软骨的修复能力，我们还利用大鼠模型研究了股骨膝关节软骨表面缺陷后的早期过程。在妊娠第19天的胎儿，软骨细胞和细胞外基质在损伤后48h内对表面缺陷都有显著的反应。藏红花素O染色显示，伤后1h，创面周围细胞外基质的部分成分发生改变，并在24小时内从有限区域扩散至整个膝关节软骨。伤后1~6h，创面周围软骨细胞c-fos表达呈一过性升高。伤口在出生后1天，即受伤72小时后仍然存在，但在出生后10天完全修复。相反，在12周龄的成人关节软骨损伤后48小时内，既没有观察到明显的反应，也没有观察到瞬时的c-fos表达。