BMP Signaling on Cartilage Repair Response in Full-thickness Articular Cartilage Defects

我们研究了BMP信号在全层关节软骨缺损软骨修复反应中的作用。在之前的研究中，我们建立了大鼠模型来阐明软骨修复反应全层关节软骨缺损。采用小缺损（0.7mm宽）和大缺损（1.5mm宽）大鼠模型，分别于术后2、4、7、14天采用免疫染色和原位杂交法分析缺损中心的修复过程。术后2天，在小缺损中心发现BMP-4信使RNA，但未观察到该蛋白。在此之后，BMP-4的信使RNA和蛋白在各个时期都被发现。术后第7天首次发现BMP-6的信使RNA和蛋白。GDF-5的信使RNA和蛋白在术后第4天出现。这些受体的信使RNA和蛋白在各个时期都有表达。另一方面，在一个大的缺损中心，术后2天发现BMP-4的信使RNA没有蛋白。术后第4天，BMP-4信使RNA及蛋白均有轻微表达。术后7天仅观察BMP-4信使RNA。术后7 d未见BMP-4信使RNA及蛋白表达。未观察到BMP-6和GDF-5的信使RNA和蛋白。这些受体的信使RNA和蛋白质在所有时期以及小缺陷中都被发现。本研究结果证实，在全层关节软骨缺损的软骨修复过程中，BMP-4信号在启动过程中起重要作用，BMP-6信号可能参与软骨细胞成熟和肥大过程，GDF-5信号可能参与软骨细胞肥大过程

We investigated BMP signaling on cartilage repair response in full-thickness articular cartilage defects. In the previous study, we established a rat model to clarify cartilage repair response full-thickness articular cartilage defects. The repair process in the center of the defects was analyzed by immunostaining and in situ hybridyzation method at 2,4,7,14 days after surgery using our rat model with a small defect (0.7mm width) and a large defect (1.5mm width). In the center of a small defect, at 2 days after surgery, the messenger RNA of BMP-4 was found, but this protein was not observed. After that, the messenger RNA and protein of BMP-4 was found through all periods. The messenger RNA and protein of BMP-6 was first found at 7 days after surgery. The messenger RNA and protein of GDF-5 was slightly first found at 4 days after surgery. The messenger RNA and protein of those receptors was expressed through all periods. On the other hand, in the center of a large defect, at 2 days after surgery, the messenger RNA of BMP-4 was found without no protein. At 4days after surgery, the messenger RNA and protein of BMP-4 was slightly expressed. At 7 days after surgery, the messenger RNA of BMP-4 was only observed. At 7 days after surgery, the messenger RNA and protein of BMP-4 were not found. The messenger RNA and protein of BMP-6 and GDF-5 was not observed through all periods. The messenger RNA and protein of those receptors was found through all periods as well as those in a small defects. Based on the results of this study, it was certified that, on cartilaginous repair in full-thickness articular cartilage defects, BMP-4 signaling is important for the initiation of the process, BMP-6 signaling may be involved in chondrocyte maturation and hypertrophy, GDF-5 signaling may be involved in chondrocyte hypertrophy