Specific RANK Cytoplasmic Motifs Drive Osteoclastogenesis.

ABSTRACT: Upon receptor activator of NF-κB ligand (RANKL) binding, RANK promotes osteoclast formation through the recruitment of tumor necrosis factor (TNF) receptor-associated factors (TRAFs). In vitro assays identified two RANK intracellular motifs that bind TRAFs: PVQEET^560-565 (Motif 2) and PVQEQG^604-609 (Motif 3), which potently mediate osteoclast formation in vitro. To validate the in vitro findings, we have generated knock-in (KI) mice harboring inactivating mutations in RANK Motifs 2 and 3. Homozygous KI (RANK^KI/KI ) mice are born at the predicted Mendelian frequency and normal in tooth eruption. However, RANK^KI/KI mice exhibit significantly more trabecular bone mass than age- and sex-matched heterozygous KI (RANK^+/KI ) and wild-type (RA

SUBMITTER: Li Y 

PROVIDER: S-EPMC6813862 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature