Deconstructing IκB kinase

On page 1677, Ruocco et al. show that the formation of bone-resorbing osteoclasts is crippled when the β subunit of the NF-κB–activating IκB kinase (IKK) complex is missing. The absence of IKKβ also protected mice against inflammatory-induced bone loss, a complication of inflammatory diseases such as rheumatoid arthritis (RA) that is caused by excessive activation of osteoclasts.

The osteoclast growth factor RANKL (receptor activator of NF-κB ligand) activates the transcription factor NF-κB, which promotes osteoclast development. NF-κB activation requires the upstream IKK complex (IKKα, β, γ), which releases NF-κB from its inhibitor protein. Although a recent report showed that the IKK complex is required for osteoclast development, the relative importance of the two catalytic subunits of IKK (α, β) in this process remained unclear.

Ruocco et al....