DISTINCT AND OVERLAPPING PATTERNS OF LOCALIZATION OF BONE MORPHOGENETIC PROTEIN (BMP) FAMILY MEMBERS AND A BMP TYPE-II RECEPTOR DURING FRACTURE-HEALING IN RATS

Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are tho ught to play an important role in bone morphogenesis. The purpose of t his study was to determine the locations of BMP-2/-4, osteogenic prote in-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) dur ing 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 thick ened 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 chondrocyte s, and was strong in fibroblast-like spindle cells and proliferating c hondrocytes in endochondral bone, On day 14 after fracture, staining w ith OP-1 antibody disappeared in proliferating and mature chondrocytes , while BMP-2/-4 staining continued in various types of chondrocytes u ntil 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 i n both intramembranous ossification and endochondral ossification. Add itionally, immunostaining for BMP-2/-4 and OP-1 was observed in multin ucleated osteoclast-like cells on the newly formed trabecular bone, al ong with BMPR-II. In reference to our precious study of BMP type I rec eptors (BMPR-IA and BMPR-IB), BMPR-II was found to be co-localized wit h 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 ossificatio n, while BMP-2/-4 acts throughout this process, Thus, these findings s uggested that BMPs acting through their BMP receptors mag play major r oles in modulating the sequential events leading to bone formation, (C ) 1998 by Elsevier Science Inc. All rights reserved.