The mechanism of bone induction and bone healing by human osteosarcoma cell extracts.
Saos-2 cultured human osteosarcoma cells contain an extractable bone inducing agent that can induce heterotopic bone in the muscle of Nu/Nu mice. A semipurified GuHCl extract of Saos-2 cells also can promote healing and complete bony union in otherwise non-healing surgically induced defects of rat femur. Northern blot analyses indicate expression of mRNAs for bone morphogenetic proteins (BMP)-1, 2, 3, 4, 6 and transforming 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 and TGF beta, whereas U20S cells expressed higher levels of BMP-2, 6 and 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 admixture 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 indication of being permanent and self-sustaining. This suggests a fundamental difference between heterotopic and orthotopic osteoprogenitor cells with those involved in orthotopic bone repair more closely resembling the committed or determined osteoprogenitor cells of marrow as described by Friedenstein.
Anderson
H C
HC
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City 66160, USA.
Hsu
H H
HH
Raval
P
P
Hunt
T R
TR
Schwappach
J R
JR
Morris
D C
DC
Schneider
D J
DJ
D000818:Animals; D015152:Blotting, Northern; D001846:Bone Development; D019485:Bone Morphogenetic Proteins; D001859:Bone Neoplasms / Q000737:chemistry* / Q000473:pathology; D001861:Bone Regeneration; D015870:Gene Expression; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000737:chemistry* / Q000473:pathology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D006133:Growth Substances; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta