THE MECHANISM OF BONE INDUCTION AND BONE HEALING BY HUMAN OSTEOSARCOMA CELL-EXTRACTS

Saos-2 cultured human osteosarcoma cells contain an extractable bone i nducing agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A semipurified GuHCl extract of Saos-2 cells also can promote he aling and complete bony union in otherwise nonhealing surgically induc ed defects of rat femur. Northern blot analyses indicate expression of mRNAs for bone morphogenetic proteins (BMP)-1, 2, 3, 4, 6 and transfo rming growth factor beta (TGF beta) in Saos-2 cells, and BMP-2, 3, 4, 5, 7 and TGF beta in nonosteoinductive U20S human osteosarcoma cells. Saos-2 cells exceeded U20S cells in expression levels of BMP-1, 3, 4 a nd TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 an d also expressed trace amounts of BMP-5 and 7 not seen in Saos-2 cells . The authors hypothesize that Saos-2 cells contain an optimal admixtu re of known bone growth factors plus possible other unknown components that, acting alone or in combination with bone morphogenetic protein and/or TGF beta, can induce bone. Although bone inducing agent-induced heterotopic bones have half lives of only a few weeks, the reparative bone induced by bone inducing agent in femoral defects gives every in dication of being permanent and self-sustaining. This suggests a funda mental difference between heterotopic and orthotopic osteoprogenitor c ells with those involved in orthotopic bone repair more closely resemb ling the committed or determined osteoprogenitor cells of marrow as de scribed by Friedenstein.