Receptor activator of NF-κB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein

Low-density Lipoprotein Receptor Deficiency Causes Impaired Osteoclastogenesis and Increased Bone Mass in Mice because of Defect in Osteoclastic Cell-Cell Fusion

“…When various doses of LDL were added to medium containing LR-FBS, osteoclast formation was partially restored in the culture in a dose-dependent manner (Fig. 1A), as reported previously (40). Similar to the effect of exogenous addition of native LDL, ox-LDL also dosedependently rescued the reduced osteoclast formation (Fig.…”

“…More recently, we found that during osteoclastogenesis, RANKL induces the expression of caveolin-1 (Cav-1) (40), a principal scaffolding protein of lipid rafts and caveolae. Furthermore, depletion of exogenous LDL causes impaired NFATc1 activation and consequently reduces osteoclast formation (40), consistent with other studies (29,30). These results suggest a tight correlation between osteoclast differentiation and cholesterol.…”

“…In addition, osteoclasts formed from LDLRdeficient precursors were smaller than wild-type osteoclasts, and the LDLR-deficient osteoclasts contained fewer nuclei, indicating impaired cell-cell fusion of osteoclast lineage cells. One possible mechanism underlying this cell fusion defect is that the lack of the LDLR gene results in abnormalities in signal transduction pathways necessary for osteoclast formation, as we reported previously that methyl-␤-cyclodextrin-mediated depletion of cholesterol from the plasma membrane and destruction of lipid rafts caused alterations in signal transduction related to osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulation (40). Removal of exogenous lipoproteins from the culture medium recapitulated this abnormal signaling and also resulted in reduced osteoclast formation because of the delayed expression of NFATc1 in preosteoclasts (40).…”

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

“…Some of our results are in agreement and disagreement with the data shown in some previous studies in which the effects of Cav-1 deficiency on bone were investigated (39,40). In the paper by Rubin et al (39), distal femur metaphysis of 8-weekold Cav-1 Ϫ/Ϫ male mice showed increased trabecular BV/TV with an apparently paradoxical decrease in MAR compared with WT mice.…”

“…6A). Radiological and histomorphometric analyses of Cav-1 Ϫ/Ϫ mice were not carried out in the study by Hada et al (40).…”