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

BMP 信号对全层关节软骨缺损软骨修复反应的影响

基本信息

批准号：
12671425
负责人：
NAKAMURA Eiichi
金额：
$ 1.98万
依托单位：
Kumamoto 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-12671425/
关键词：
Articular Cartilage Bone Morphogenetic Protein Chondrocyte 骨形戒因子

项目摘要

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

我们研究了BMP信号在全层关节软骨缺损修复反应中的作用。在之前的研究中，我们建立了一种大鼠模型，以阐明软骨修复反应对关节软骨全层缺损的影响。分别于术后2、4、7、14天用免疫组织化学和原位杂交法分析小面积(0.7 mm宽)和大面积(1.5 mm宽)缺损区中心的修复过程。在小缺损区中央，术后2天可见BMP-4的信使RNA，但未观察到该蛋白。此后，BMP-4的信使RNA和蛋白在各个时期均可检测到。术后7d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4天开始出现。这些受体的信使RNA和蛋白在各个时期都有表达。另一方面，在大的缺损区的中心，术后2天，BMP-4的信使RNA没有发现蛋白。术后4天，BMP-4的信使RNA和蛋白有微弱表达。术后7d，仅观察到BMP-4的信使RNA。术后7d，未见BMP-4的信使RNA和蛋白表达。BMP-6和GDF-5的信使RNA和蛋白并未在整个发育过程中观察到。这些受体的信使RNA和蛋白在所有时期都有发现，也有一些小的缺陷。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信号在软骨修复过程中起重要作用，BMP-6信号可能参与软骨细胞的成熟和肥大，GDF-5信号可能参与软骨细胞肥大。