Abstract
To investigate the role of recombinant human bone morphogenetic protein 2 (rhBMP-2) in the differentiation of osteoblasts and chondrocytes from mesenchymal progenitors, the effects of rhBMP-2 on differentiation of C3H10T1/2 pluripotent cells and MC3T3-E1 osteoblastic cells were examined. When C3H10T1/2 cells were treated with rhBMP-2, they differentiated into osteoblastic cells with alkaline phosphatase (ALP) activity and specific immunoreactivity for type I collagen and osteocalcin, and also chondrocytes immunoreactive with type h collagen appeared. RhBMP-2 also induced production of para thyroid hormone (PTH) -dependent cAMP in C3H10T1/2 cells. When C3H10T1/2 cells were transplanted into the peritoneal cavity of athymic mice using rhBMP-2-containing diffusion chambers, they generated both bone and cartilage in the diffusion chambers. RhBMP-2 also stimulated ALP activity and production of PTH-dependent CAMP and osteocalcin in MC3T3-E1 cells, but did not induce chondrocytes. MC3T3-E1 cells trans-planted in rhBMP-2-containing diffusion chambers formed only bone in the diffusion chambers. These results suggested that rhBMP-2 stimulates differentia-tion of both osteoblasts and chondrocytes, but its effects depend on the stage of differentiation of the target cells.