Caveolin-1 Regulates Osteoclastogenesis and Bone Metabolism in a Sex-dependent Manner [Metabolism]

January 5th, 2015 by Lee, Y. D., Yoon, S.-H., Park, C. K., Lee, J., Lee, Z. H., Kim, H.-H.

Lipid raft microdomains have important roles in various cellular responses. Caveolae are a specialized type of lipid rafts that are stabilized by oligomers of caveolin proteins. Here we show that caveolin-1 (Cav-1) plays a crucial role in the regulation of osteoclastogenesis. We found that caveolin-1 was dramatically up-regulated by receptor activator of nuclear factor κB ligand (RANKL), the osteoclast differentiation factor. Knockdown of Cav-1 reduced osteoclastogenesis and induction of NFATc1, the master transcription factor for osteoclastogenesis, by RANKL. Consistent with in vitro results, injection of caveolin-1 siRNA onto mice calvariae showed reduction in RANKL-induced bone resorption and osteoclast formation. Moreover, Cav-1-/- female mice had higher bone volume and lower osteoclast number compared to wild type mice. However, Cav-1-/- male mice had both osteoclast and osteoblast numbers higher than wild type mice with no difference in bone volume. The sex dependency in the effect of Cav-1 deficiency was partly attributed to decreased RANK and increased cFms expression in osteoclast precursors of female and male mice, respectively. Taken together, these data demonstrate that Cav-1 has a complicated, but critical role, for osteoclastogenesis.