Endogenous bone morphogenetic protein: immunohistochemical localization in repair of a punch hole in the rabbit's ear.

By means of monoclonal anti-bone morphogenetic protein 2 immunohistochemical methods, endogenous bone morphogenetic protein was observed in the process of generation of heterotopic bone in experimental punch holes in the rabbit's ear. In repair of the punch hole, dermis, subcutaneous connective tissue, and perichondrium proliferated, hypertrophied, and differentiated in the rim within 2 weeks. By 3 to 4 weeks, epidermis grew centripetally down into and across the dorsal and ventral openings and sealed the punch hole. A blastema-like structure consisting of a condensation of the mesenchymal type cells covered the cut ends of the elastic cartilage. The condensation differentiated into chondro-osteoprogenitor cells and hyaline cartilage within 4 to 5 weeks. Within 4 to 6 weeks, sprouting capillaries, macrophages, and monocytes resorbed and replaced hyaline cartilage with a perichondral ring of bone. Anti-bone morphogenetic protein 2 appeared first in the perichondrium, then in the condensation, and later in the chondro-osteoprogenitor cells. A basic assumption was that latent non-reactive bone morphogenetic protein was converted to the anti-bone morphogenetic protein 2-reactive form by injury, inflammation, and proteolysis. The reactive form and various other local factors contributed the temporal and spatial constraints of a morphogenetic field for development of heterotopic bone. The receptors and mechanism of bone morphogenetic protein signal transduction are unknown.