ENHANCED EXPRESSION OF TYPE-I RECEPTORS FOR BONE MORPHOGENETIC PROTEINS DURING BONE-FORMATION

Type I receptors for bone morphogenetic proteins (BMPs), i.e., BMPR-IA and BMPR-IB, are transmembrane serine/threonine kinases, that bind os teogenic protein-1 (OP-1, also termed BMP-7) and BMP-4. Using antibodi es specific to BMPR-IA and -IB, we have studied the expression of BMP type I receptors in the bone formation process during embryonic develo pment and fracture healing, In the mouse embryo, both BMPR-IA and -IB were expressed in condensing mesenchymal cells at 13.5 days post coitu m (p.c.). At 15.5 days p.c., expression of BMPR-IB, but not of BMPR-IA , was observed in the cells in perichondrium of developing cartilage. At 17.5 and 19.5 days p.c., expression of both receptors was observed in chondrocytes and in osteoblasts. In normal rat adult bone, expressi on of BMPR-IA, but not of BMPR-IB, was observed in osteoblasts in the periosteum. Three days after the femoral fracture, expression of BMPR- IA and -IB was up-regulated in cells at the proliferating osteogenic l ayer of the periosteum. On day 7, both receptors were found in fibrobl ast-like spindle cells and chondrocytes in the endochondral ossificati on sites, and osteoblasts in the newly formed trabecular bone. Express ion of BMPR-IA was higher than that of BMPR-IB in osteogenic layer on day 3 and in osteoblasts in the trabecular bone on day 7. On day 14, e xpression of BMP type I receptors was observed at similar sites, albei t with lower expression levels than were observed on day 7, The presen t data suggest that expression of BMP type I receptors is up-regulated during bone formation, and that they may play important roles in bone morphogenesis.