IKKbeta activation is sufficient for RANK-independent osteoclast differentiation and osteolysis.

ABSTRACT: Monocytes differentiate into osteoclasts through stimulation of receptor activator of NF-kappaB (RANK). Many downstream effectors of RANK play a positive role in osteoclastogenesis, but their relative importance in osteoclast differentiation is unclear. We report the discovery that activation of a single pathway downstream of RANK is sufficient for osteoclast differentiation. In this regard, introduction of constitutively activated IKKbeta (IKKbeta(SSEE)) but not wild-type IKKbeta into monocytes stimulates differentiation of bona fide osteoclasts in the absence of RANK ligand (RANKL). This phenomenon is independent of upstream signals because IKKbeta(SSEE) induced the development of bone-resorbing osteoclasts from RANK and IKKalpha knockout monocytes and in conditions in which NEMO-IKKbeta

SUBMITTER: Otero JE 

PROVIDER: S-EPMC3153134 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature