title: Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, Kagoshima University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Onishi
authors.forename: Y
authors.initials: Y
authors.lastname: Ishidou
authors.forename: T
authors.initials: T
authors.lastname: Nagamine
authors.forename: K
authors.initials: K
authors.lastname: Yone
authors.forename: T
authors.initials: T
authors.lastname: Imamura
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: T K
authors.initials: TK
authors.lastname: Sampath
authors.forename: P
authors.initials: P
authors.lastname: ten Dijke
authors.forename: T
authors.initials: T
authors.lastname: Sakou
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000502:physiology; D002455:Cell Division; D019902:Chondrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D007150:Immunohistochemistry; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C498220:Bmpr2 protein, rat; D052006:Bone Morphogenetic Protein Receptors, Type II