Ectopic and orthotopic osteogenesis induced by BMP-7 in rat

Members of transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily induce endochondral and/or int4amembranous b one formation in vivo. Present study describes the efficiency BMP-7 when implanted with demineralized bone matrix carrier (IRBR) at ectopic sites in rat. Osteogenesis induced by IRBR with and without BMP-7 implanted subcutaneously in thoracic region, onto calvarial defect and intact calvariae has been studied from days 7 to 21 after implantation. Implants were separated from surrounding tissue, fixed in 4% paraformaldehyde, embedded undecalcified in MMA, cut serially at 500 micrometer intervals on 3-4 micrometer slices, and were analyzed at days 7, 14, and 21 by histologic, histochemic, histomorphometric, and immunohistochemic methods. Results showed that only IRBR implants with BMP-7 were osteoinductive. Histologic and hystomorphometric studies demonstrated that BMP-7 induced chondrogenesis at subcutaneous site and ossteogenesis at calvaria site on day 7. On day 21 all implants consisted mainly of bone with more pronounced osteogenesis observed in both calvarial sites. Immunohistochemical analysis revealed BMP-7 positive staining at subcutaneous sites in hypertrophic chondrocytes, infiltrate cells and fibrous membrane. BMP-3 positive staining was observed as less intense in infiltrate cells and fibrous membrane. These results suggest that BMPs induced endochondral and intramembranous osteogenesis when implanted on subcutaneous and calvarial sites, respectively.