Vitamin E decreases bone mass by stimulating osteoclast fusion

Abstract

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that 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. Here, we show that mice deficient in α-tocopherol transfer protein (Ttpa(-/-) mice), a mouse model of genetic vitamin E deficiency, have high bone mass as a result of a decrease in bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of its antioxidant capacity, 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 abnormality seen in Ttpa(-/-) mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol-supplemented diet, which contains a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.

Bu-Shen-Ning-Xin decoction suppresses osteoclastogenesis <i>via </i>increasing dehydroepiandrosterone to prevent postmenopausal osteoporosis

“…A primary osteoclast culture and osteoclastogenesis in vitro was accomplished as previously described (10). Briefly, bone marrow-derived monocyte/macrophage precursor cells (BMMs) from the femurs and tibias of 20-week-old mice in the OVX group were cultured in MEM without phenol red supplemented with FBS in the presence of 10 ng/mL M-CSF for 2 days.…”

Vitamin E slows down the progression of osteoarthritis

“…In animals, vitamin E deficiency causes derangement of nucleic acid metabolism (30,31). These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.…”

“…In a study conducted by Baskin et al (32), following 3 days of endurance training in sled dogs, supplementation with vitamin E and lutein for 1 month was associated with a reduction in oxidative DNA damage, as demonstrated by decreased levels of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OHdG) in the plasma, whereas untreated dogs showed an increase in 8-OHdG levels. Various nuclear changes can be observed in tissues that are severely affected by a deficiency of vitamin E (30). Cell-based assays demonstrated that α-tocopherol stimulates osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein.…”

“…Cell-based assays demonstrated that α-tocopherol stimulates osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein. This protein is an essential molecule for osteoclast fusion, which occurs via the activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as via its direct recruitment to the Tm7sf4 promoter (a gene encoding DC-STAMP) (30). There is a strong hereditary component to osteoarthritis, reflected by high heritability estimates from twin studies (33).…”

Antioxidant Function and Health Implications of Vitamin E

“…In another highly publicized recent article, Fujita et al [73] report that mice deficient in α-tocopherol transfer protein (Ttpa-/-mice), a mouse model of genetic vitamin E deficiency, have high bone mass due to a decrease in bone resorption, and that wild-type mice or rats fed an α-tocopherol-supplemented diet lost bone mass. The findings suggest that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion, and that vitamin E supplements intended to reduce health risk may also cause thinning of bones.…”