The Effects of Endogenous BMP During The Process of BMP-Induced Bone Formation and A Possibility of Clinical Application

Abstract

The participation of endogenous BMP-2 in the process of ectopic osteoinduction by rhBMP-2 implanted into rat muscles was investigated using immunohistochemistry, immunoelectron microscopy, in situ hybridization and real-time RT-PCR. Our results suggested that not only implanted exogenous rhBMP-2 but also endogenous BMP-2 produced by osteogenic and/or chondrogenic cells participates in the rapid progression of ectopic bone formation cascade. Since the statins promote the expression of endogenous BMP-2 and enhance the bone formation, we next examined the stimulative effect of statins on the rhBMP-2-induced osteogenesis, by radiological and biochemical analysis, and histology. These results indicated that subcutaneously injected simvastatin promotes rhBMP-2-induced ectopic bone formation by reducing bone turnover. Simvastatin may become a useful adjuvant therapy for enhancing BMP-2 induced bone formation.