Effects of Tumor Necrosis Factor on Bone Formationin Vitro*

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Abstract
Tumor necrosis factor (TNF) was studied for its effects on bone formation in cultured rat calvariae. TNF.alpha. at 100-100,000 U/ml stimulated [3H]thymidine incorporation into DNA, an effect that appeared after 24 h of treatment and lasted 96 h. Transient (24-h) treatment with TNF.alpha. increased [3H]proline incorporation into type I collagen 24-72 h after the factor was removed; this effect was DNA synthesis dependent and blocked by hydroxurea. Transient treatment with TNF.alpha. also increased alkaline phosphatase activity. In contrast, continuous treatment with TNF.alpha. for 48-96 h caused a marked inhibition on [3H]proline incorporation into type I collagen and alkaline phosphatase activity. TNF.alpha. caused a small increase in collagen degradation. Lymphotoxin had similar effects to those of TNF.alpha.. In conclusion, TNF.alpha. stimulates calvarial DNA synthesis which causes an increased number of collagen-synthesizing cells, but TNF.alpha. has a direct inhibitory effect on osteoblastic function.