Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor beta superfamily implicated by gene ablation studies in several critical processes in early mouse development. BMP-2 plays an essential role not only in embryonic stem cell differentiation, but also in mesenchymal stem cell differentiation and bone formation.
Studies of mouse embryonic stem cell differentiation in vitro adduced evidence for a critical role for BMP-2 in the differentiation of extra-embryonic endoderm, and in the cavitation of the embryo, the process whereby programmed cell death in a subpopulation of the pluripotent stem cells of the inner cell mass leads to the formation of the egg cylinder. This study further showed that BMP-2 transcripts were expressed in the extra-embryonic endoderm, a finding that has recently been confirmed in a study which defined a role for this molecule in the induction of primordial germ cells.
A screen for factors affecting growth and differentiation of human pluripotent embryonal carcinoma cells revealed that BMP-2 induced differentiation of the cells into a flattened, epithelial squamous cell displaying an immunophenotype and gene expression profile similar to extra-embryonic endoderm.
Cells that morphologically resemble the flat epithelial cells induced in human EC cultures by BMP-2 also appear spontaneously in human embryonic stem cultures grown under standard conditions
Gene therapy studies show that bone defects are healed by the implantation of a bioresorbable polymer mixed with bone marrow mesenchymal stem cells to which adenovirus BMP-2 is transferred. Systemic administration of rhBMP-2 increases mesenchymal stem cell activity and reverses ovariectomy-induced and age-related bone loss in two different mouse models. These results suggest that BMP-2 may be utilized for the treatment of osteoporosis. Recent studies show that rhBMP-2 delivered in an injectable formula with a calcium phosphate carrier or with a liposome carrier accelerates bone healing in a rabbit ulna osteotomy model and a rat femoral bone defect model. Recent clinical studies show that rhBMP-2 can be used as complete bone graft substitutes in spinal fusion surgery. In some circumstances, the efficacy of BMP-2 for inducing successful fusion is superior to that of autogenous bone graft. BMP-2 is shown to be efficacious in several fusion applications, including intervertebral and lumbar
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