Bone histogenesis mediated by nonosteogenic cells.

Abstract

Intramuscular implantation of several established, nonfibroblastic epithelial cell lines of various origin causes endochondral ossification at the site of cell graft. Heterotopically-induced bone is also a site of myelopoiesis. Myelohistograms of ectopic bone marrow do not differ substantially from that of marrow present in orthotopic (skeletal) bones. Heterotopically-induced bones are not covered by a periosteal membrane with a functioning cambium layer. The nature of the bone-inducing principle of epithelial cells is not known as yet, although it was established that cells able to induce heterotopic bone formation are characterized by a high alkaline-phosphatase activity and have an epithelial status. Cells responding to the osteoinducing principle are distributed among skeletal muscles and are absent in the peritoneal cavity or in the kidney parenchyma. Periosteal membranes of skeletal bones are activated by a variety of agents (Moloney sarcoma virus-induced tumors, numerous nonvirus-induced neoplasms, T-lymphocyte mitogens, and activated lymphocytes) to proliferate and lay down new bone. The same agents can also activate in vivo perichondral membranes. It is theorized that cells involved in antitumor reaction produce a chondroblast/osteoblast activating factor(s), in addition to the osteoclast-activating one.