| [ Summary ] |
Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells which are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitamin E in bone remodeling is unknown. We exhibit information illustrating that mice deficient in α-tocopherol transfer protein (Ttpa-/- mice), a mouse model of genetic vitamin E deficiency, have high bone mass levels as a result of decreased bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of antioxidant capacity. This is accomplished by inducing the expression of dendritic-cell-specific transmembrane protein, an essential molecule for osteoclast fusion, through activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as its direct recruitment to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormalities seen in Ttpa-/- mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol‒ supplemented diet which contained a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is determinantal to bone mass maintenance thorough regulation of osteoclast fusion. |