RANKL-independent osteoclastogenesis in the SH3BP2 cherubism mice.

Even though the receptor activator of the nuclear factor-κB ligand (RANKL) and its receptor RANK have an exclusive role in osteoclastogenesis, the possibility of RANKL/RANK-independent osteoclastogenesis has been the subject of a long-standing debate in bone biology. In contrast, it has been reported that calvarial injection of TNF-ɑ elicits significant osteoclastogenesis in the absence of RANKL/RANK in NF-κB2- and RBP-J-deficient mice, suggesting that inflammatory challenges and secondary gene manipulation are the prerequisites for RANKL/RANK-deficient mice to develop osteoclasts . Here we report that, even in the absence of RANKL ( ), cherubism mice ( ) harboring the homozygous gain-of-function mutation in SH3-domain binding protein 2 (SH3BP2) develop tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts spontaneously.