Osteoprotegerin mRNA is increased by interleukin-1 alpha in the human osteosarcoma cell line MG-63 and in human osteoblast-like cells. Osteoprotegerin (OPG) is a soluble receptor for the Osteoprotegerin-Ligand (OPGL) which is expressed on osteoblasts and mediates the signal for osteoclast differentiation. In the present study we demonstrate that OPG mRNA levels in MG-63 cells are increased in a dose-dependent manner after 8 h of treatment with IL-1 alpha (338 +/- 53% over control at 25 U/ml). Interleukin-6 (IL-6), under similar culture conditions, does not affect OPG mRNA levels. Time-course studies show that IL-1 alpha (25 U/ml) causes a transient increase of OPG mRNA levels in MG-63 cells, peaking after 4 h of treatment. An increase of the OPG transcript occurs in hOB cells at 0.5 h which is still present after 24 h of IL-1 alpha treatment. In MG-63 cells neither basal-nor IL-1 alpha-induced OPG mRNA levels are altered by the translational inhibitor cycloheximide. These results suggest that expression of OPG in osteoblasts may be regulated by IL-1 alpha.