Several members of the fibroblast growth factor family have an important role in development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast specific ALP production, bone nodule formation and calcium accumulation, if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated proliferation of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF-8b. In addition, the heparin-binding growth factor fraction (HBGF) of Shionogi 115 (S115) mouse breast cancer cells that express and secrete fibroblast growth factor 8 (FGF-8) at a very high level had similar effect in bone marrow cultures as exogenous FGF-8. Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone and cartilage formation as demonstrated by typical histology and expression of markers specific for cartilage (type II and IX collagen) and bone (osteocalcin).

These results demonstrate that FGF-8 effectively predetermines bone marrow cells to differentiate to osteoblasts and increases bone formation in vitro. It is possible that FGF-8 also stimulates bone formation in vivo. The results further suggest that FGF-8 expressed by a great proportion of malignant breast and prostate tumors may, among other factors, also be involved in formation of osteosclerotic bone metastases.