Bone morphogenetic protein-2 is markedly synergistic with tumor necrosis factor in stimulating the production of nerve growth factor in fibroblasts.

A possible interaction between tumor necrosis factor (TNF) and transforming growth factor-beta (TGF-beta) superfamily cytokines in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. Although TGF-beta 1 and Activin A stimulated NGF production in Swiss 3T3 cells, they antagonized the stimulatory effect of TNF on fibroblast NGF production when used in combination. On the contrary, TNF's stimulatory activity on fibroblast NGF production was markedly synergized by bone morphogenetic protein-2 (BMP-2); BMP-2 by itself did not stimulate NGF production in the cells. These findings suggest that BMP-2, in concert with TNF, plays an essential role in regulating the regeneration of peripheral nerves following injury with bone fracture through an indirect mechanism by which it stimulates NGF production in fibroblasts.