Osteoblasts undergo a process of proliferation and differentiation and are responsible for hone formation. In this study, we examined the relation between NF-kappaB, a key transcription factor in bone metabolism, and osteoblast maturation. NF-kappaB activity and expression of p50, a subunit of NF-kappaB, decreased during development of osteoblastic MC3T3-E1 cells. The secretion of IL-6 by osteoblast, which in combination with soluble IL-6 receptor induces conversion of fibroblasts to alkaline phosphatase-positive cells, also increased. p50 antisense oligonucleotide increased IL-6 mRNA expression. These results suggest that p50 regulates transcription of IL-6 and indirectly controls osteoblast maturation.