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Biomolecular analysis on bone formation mechanism of ossification of the posterior longitudinal ligament. -The roles of transforming growth factor-beta and bone mophogenetic protein-

后纵韧带骨化成骨机制的生物分子分析

基本信息

批准号：
07671604
负责人：
SAKOU Takashi
金额：
$ 1.54万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

In ossified tissue including non-ossified ligaments from the patients with cervical OPLL and normal ligaments from the patients with cervical disc herniation, we examined the immunohis-tological expression of BMP receptor type IA,IB and II (BMPR-IA,-IB and II). Spindle shaped cells and oval shaped cells were observed within the non-ossified ligament, and natured and hypertrop-hic chondrocytes were observed in the transitional zone between non-ossified ligament and ossif-ied tissue. It suggested that ossified foci was formed mainly through endochondral ossification process. The expression of BMPR-IA,-IB and -II was detected not only in chondrocytes but also in ligament cells. These findings were not observed in the ligaments from the patients with cer-vical disc herniation. The result suggested that the ligament cells of OPLL patients had been transforming into bone-forming cells possessing high reactivity to BMPs.We futheromore investigated about the expression of BMP-2/-4 and osteogenic protein-1 (OP-1/BMP-7), and their receptors : BMPR-IA,-IB and -II,and activin receptor type I and II (ActR-I and-II), during rat fracture healing process and in articular cartilage. BMPs and their receptors were expressed in various stages of intramembranous ossification and endochondral ossification, which suggested that cartilage and bone formation process was regulated by various BMPs signals via diverse receptor complex. Expression of BMPs and their receptors were also observed in articular chondrocytes. Our sudies clarified that BMPs and their receptors play the critical roles in various cellular events during physiological bone formation process, and in pathogenesis and development of pathological ectopic ossification. In the furture, our results appear to contribute for biomolecular approach on inhibition of ectopic bone formation.

在骨化组织包括颈椎OPLL患者的非骨化韧带和颈椎间盘突出症患者的正常韧带中，我们检测了BMP受体IA、IB和II型（BMPR-IA、-IB和II）的免疫组织学表达。在未骨化韧带内可见梭形细胞和椭圆形细胞，在未骨化韧带与骨化组织之间的过渡区可见自然肥大的软骨细胞。提示骨化灶主要通过软骨内骨化过程形成。BMPR-IA、-IB和-II不仅在软骨细胞中表达，而且在韧带细胞中也有表达。在颈椎间盘突出症患者的韧带中未观察到这些发现。本实验进一步研究了骨形态发生蛋白-2/-4和成骨蛋白-1（OP-1/BMP-7）及其受体BMPR-IA、-IB和-II，以及激活素受体I型和II型（ActR-I和-II）在大鼠骨折愈合过程和关节软骨中的表达。骨形成蛋白及其受体在膜内成骨和软骨内成骨的不同阶段均有表达，提示软骨和骨形成过程受不同的骨形成蛋白信号通过不同的受体复合物调控。骨形成蛋白及其受体在关节软骨细胞中也有表达。我们的研究阐明了BMPs及其受体在生理性骨形成过程中的各种细胞事件以及病理性异位骨化的发生发展中起着关键作用。本研究结果为从生物分子水平抑制异位骨形成提供了理论依据。