Objective To explore the interaction of FGF-2 and BMP-2 in osteoblastic differentiation of calvarial suture cells. Methods Neonatal calvarial suture cells of SD rat were harvested. FGF-2 was added into cell cultures and BMP-2 expression in cranial suture cells was observed. Meanwhile, FGF-2 and BMP-2 were both added into cell cultures and the osteoblastic differentiation of cranial suture cells was observed by ALP staining, mineralized nodule staining and qPCR. Then Noggin was added to observe the changes of cells’ osteoblastic differentiation. Results BMP-2 expression increased in a time-dependent manner after the cells treated with FGF-2 and increased in a dose-dependent manner up to 50 ng/ml FGF-2, after which BMP-2 expression reached a plateau;After FGF-2 and BMP-2 co-stimulation, the expression of early marker of osteoblast differentiation (COL-1) was decreased while the expression of late markers (ALP, OC and BSP) were increased to accelerate mineralization. The natural BMP antagonist Noggin inhibited the expression of FGF2-induced OC and BSP by 1.40-fold and 1.41-fold respectively, and inhibited the expression of FGF2- and BMP2-induced OC and BSP by 1.26-fold and 1.20-fold respectively. Conclusion BMP2 is a downstream target of FGF-2, and BMP-2 signals are required for FGF-2-dependent induction of later-stage osteoblast differentiation in cranial suture cells.