Novel functions for NFκB: inhibition of bone formation

The role of the transcription factor NFκB in osteoclasts and bone degradation is well understood. In this Perspectives article, the authors discuss its newly described inhibitory function in osteoblasts and bone formation, and how therapies that target NFκB might be beneficial in osteoporosis and other inflammatory bone diseases. NFκB is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NFκB in the negative regulation of bone formation. In this article, we discuss how NFκB activation affects osteoblast function and bone formation. In particular, we describe how reduced NFκB activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NFκB crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NFκB-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption.