Bone Abstracts

Lipid raft microdomains have important role in cellular signaling. Caveolae are a specialized type of lipid rafts that are stabilized by oligomers of caveolin protein. Here we showed that caveolin-1 (Cav-1) is a critical membrane structural protein of osteoclast. In microarray analysis, we found that caveolin-1 was significantly up-regulated by RANKL. Knock-down of Cav-1 in bone marrow derived-macrophage reduced osteoclastogenesis. Consistent with the in vitro results, in vivo injection of caveolin-1 siRNA into mice calvariae showed reduction of RANKL-induced bone resorption. We also found Cav-1 knock-out mice showed inhibition of bone resorption and increased bone volume. Cav-1 affects cFms and RANK expression, two major receptors for osteoclastogenesis. Interestingly, cFms expression was decreased only in protein levels, not in mRNA levels. But, RANK expression was decreased both mRNA and protein levels. It seems that caveolin-1 regulates cFms protein stability. Actually, we found that cav-1 interact with cFms. Following these event, knockdown of caveolin-1 substantially suppressed RANKL-induced MAPK and Akt signaling pathways and NFATc1, the master regulator of osteoclastogenesis. Taken together, these data demonstrate that caveolin-1 has critical role for osteoclastogenesis.