RANK IVVY motif plays crucial roles in osteoclastogenesis.

ABSTRACT: RANKL and its receptor RANK play a vital role in osteoclastogenesis. RANK primarily recruits TRAFs to promote osteoclastogenesis but also contains an TRAF-independent motif (IVVY^535-538), which mediates osteoclast lineage commitment in vitro. Here, we have developed knockin mice in which inactivating mutations are introduced in the IVVY motif (IVVY to IVAF). Homozygous knockin (RANK^AF/AF) mice are viable and born at the expected Mendelian ratio. Micro-computed tomography (μCT) and histomorphometric analyses of femurs of wild type (RANK^+/+) and RANK^AF/AF mice reveal significant increases in trabecular bone mass in RANK^AF/AF compared to age and sex matched RANK^+/+ mice due to impaired osteoclastogenesis in vivo. Bone marrow ma

SUBMITTER: Chen S 

PROVIDER: S-EPMC11761383 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature