Mouse marrow, which contains osteoblast and osteoclast precursors, was grown in the presence of calcitriol and/or basic fibroblast growth factor (FGF-2). RAW 264.7 cells were differentiated into osteoclast-like cells in the presence of receptor activator of NF-kappaB-Ligand (RANK-L) and/or FGF-2. FGF-2 alone supported osteoclastogenesis in mouse marrow cultures, but not by RAW 264.7 cells alone. Although FGF-2 supported low levels of osteoclastogenesis in mouse marrow cultures, it strongly inhibited the high levels of osteoclastogenesis triggered by calcitriol. Adding excess recombinant-RANK-L to the cultures did not relieve this inhibition. After mouse marrow osteoclasts were differentiated, FGF-2 dose-dependently inhibited bone resorptive activity. FGF-2 increased the tendency of RAW 264.7 osteoclast-like cells to fuse into very large giant cells and induced reorganizations of the actin cytoskeleton in mature, RANK-L-induced RAW 264.7 osteoclast-like cells. These results suggest that FGF-2 has both direct and indirect effects on osteoclast formation and bone resorption. (C) 2004 Elsevier Inc. All rights reserved.