Inhibition by tumor necrosis factor of induction of ectopic bone formation by osteosarcoma-derived bone-inducing substance.

The effect of tumor necrosis factor alpha (TNF-alpha) on ectopic endochondral bone formation was studied in an experimental system for bone induction using murine osteosarcoma-derived bone-inducing substance. Ectopic new bone formation was inhibited by daily administration of recombinant human TNF-alpha (20-200 micrograms/kg body weight per day, intraperitoneally) after subcutaneous implantation of the bone-inducing substance into mice. Histological examination revealed that TNF-alpha prevented mesenchymal cells from differentiating into chondrocytes in the process of endochondral bone formation. The inhibitory effect of TNF-alpha continued during the period of its administration, but not after its administration was stopped. The bone induced in a three week period after discontinuation of TNF-alpha administration was histologically normal, but smaller than that induced in control animals. These findings suggested that TNF-alpha reversibly inhibits the biological activity of the bone-inducing substance or impairs the ability of cells to respond to the bone-inducing substance at an early stage of ectopic bone formation.