Response of the rabbit metaphysis to implants of bovine bone morphogenetic protein (bBMP)

The response of protodifferentiated and differentiated bone cells to bovine bone morphogenetic protein (bBMP) was observed in implants in the adult rabbit distal femoral metaphysis. Bovine serum albumin and denatured bBMP were implanted in the contralateral femur of controls. The changes of the bone marrow reflected the reaction of protodifferentiated cells. The changes in preexisting trabecular bone tissue reflected the reaction of differentiated cells to bBMP. 45Ca radioisotope quantitative methods demonstrated that the bone morphogenetic response was superimposed upon the reaction to the injury of surgical implantation. By the end of the fourth week, roentgenograms and histologic sections showed larger deposits of intrametaphyseal cartilage and bone in bBMP than in control implanted femurs. By the end of the eighth week, bone formation was associated with remodeling of the entire distal femur and expansion of the external diameter of the metaphysis. These observations indicate the need for investigation of perisinusoid and perivascular cells of periosteum, endosteum, and marrow stroma that are undifferentiated with respect to cartilage and bone but are principal target tissues for BMP.