Local effects of bone morphogenetic protein-4 on skeletal tissues

To examine the local effects of bone morphogenetic protein-4 on diverse skeletal tissues in vivo, Chinese hamster ovary tumor cells transfected with the murine bone morphogenetic protein-4 gene were implanted into athymic nude mice by injection into the subcutaneous space of the skull, intra- and extraarticular spaces of the knee, paravertebral muscles, and intramedullary space in the femur, to form experimental tumors secreting bone morphogenetic protein-4. As a control, mock vector-transfected Chinese hamster ovary tumor cells were used. Three weeks after injection, the newly formed Chinese hamster ovary tumors together with the skeletal tissues adjacent to the tumor were recovered from each site and processed for histologic examination. On the periosteum of calvaria, new bone, but no cartilage, was observed, and abundant chondrogenic cell proliferation was seen in the apophysis of the spinous process and around Ranvier's groove in the knee. There were no apparent reactions to the Chinese hamster ovary tumors secreting bone morphogenetic protein-4 in the articular cartilage of the knee or the bone marrow of the femur. Control tumors did not elicit any bone or cartilage formation.