Onishi T, Ishidou Y, Nagamine T, Yone K, Imamura T, Kato M, Sampath T K, ten Dijke P, Sakou T
Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan.
Bone. 1998 Jun;22(6):605-12. doi: 10.1016/s8756-3282(98)00056-8.
Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to play an important role in bone morphogenesis. The purpose of this study was to determine the locations of BMP-2/-4, osteogenic protein-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) during rat fracture healing by immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II in intramembranous ossification and endochondral ossification. In the early stage of fracture repair, the expression of BMP-2/-4 and OP-1 was strongly induced in the thickened periosteum near the fracture ends, and coincided with an enhanced expression of BMPR-II. On day 7 after fracture, staining for BMP-2/-4 and OP-1 immunostaining was increased in various types of chondrocytes, and was strong in fibroblast-like spindle cells and proliferating chondrocytes in endochondral bone. On day 14 after fracture, staining with OP-1 antibody disappeared in proliferating and mature chondrocytes, while BMP-2/-4 staining continued in various types of chondrocytes until the late stage. In the newly formed trabecular bone, BMP-2/-4 and OP-1 were present at various levels. BMPR-II was actively expressed in both intramembranous ossification and endochondral ossification. Additionally, immunostaining for BMP-2/-4 and OP-1 was observed in multinucleated osteoclast-like cells on the newly formed trabecular bone, along with BMPR-II. In reference to our previous study of BMP type I receptors (BMPR-IA and BMPR-IB), BMPR-II was found to be co-localized with BMPR-IA and BMPR-IB. BMP-2/-4 and OP-1 antibodies exhibited distinct and overlapping immunostaining patterns during fracture repair. OP-1 may act predominantly in the initial phase of endochondral ossification, while BMP-2/-4 acts throughout this process. Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation.
骨形态发生蛋白（BMPs）及其受体（BMPRs）被认为在骨形态发生中起重要作用。本研究的目的是通过免疫染色确定大鼠骨折愈合过程中BMP - 2/-4、成骨蛋白-1（OP-1，也称为BMP-7）和BMP II型受体（BMPR-II）的定位，从而阐明BMPs和BMPR-II在膜内成骨和软骨内成骨中的可能作用。在骨折修复的早期，骨折端附近增厚的骨膜中BMP-2/-4和OP-1的表达被强烈诱导，并且与BMPR-II表达的增强相一致。骨折后第7天，BMP-2/-4和OP-1免疫染色在各种类型的软骨细胞中增加，并且在软骨内骨中的成纤维细胞样梭形细胞和增殖软骨细胞中较强。骨折后第14天，OP-1抗体染色在增殖和成熟软骨细胞中消失，而BMP-2/-4染色在各种类型的软骨细胞中持续到后期。在新形成的小梁骨中，BMP-2/-4和OP-1以不同水平存在。BMPR-II在膜内成骨和软骨内成骨中均有活跃表达。此外，在新形成的小梁骨上的多核破骨细胞样细胞中观察到BMP-2/-4和OP-1的免疫染色，同时还有BMPR-II。参照我们之前对BMP I型受体（BMPR-IA和BMPR-IB）的研究，发现BMPR-II与BMPR-IA和BMPR-IB共定位。在骨折修复过程中，BMP-2/-4和OP-1抗体表现出不同且重叠的免疫染色模式。OP-1可能主要在软骨内成骨的初始阶段起作用，而BMP-2/-4在整个过程中起作用。因此，这些发现表明通过其BMP受体起作用的BMPs可能在调节导致骨形成的一系列事件中起主要作用。
