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Abstract
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.