The TRAF6 binding molecule p62/SQSTM1 is a critical regulator of inflammatory bone destruction

The activation of nuclear factor κB (NFκB) via RANK is essential in regulating osteoclastogenesis. Under inflammatory conditions this process is enhanced by cytokines such as tumour necrosis factor α (TNFα). P62/SQSTM1 directly modulates these pathways through complex formation with TRAF6, aPKCs and ubiquitin. However, the role of p62/SQSTM1 in regulating bone turnover under inflammatory conditions, and specifically the role of the signal transduction domains of p62/SQSTM1, is unclear. Mice were generated that carry a shortened but functional mutant of p62 with …