Effect of vitamin K-2 on osteoblast apoptosis: Vitamin K-2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine
S. Urayama et al., Effect of vitamin K-2 on osteoblast apoptosis: Vitamin K-2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine, J LA CL MED, 136(3), 2000, pp. 181-193
Citations number
39
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Vitamin K-2 is used for the treatment of osteoporosis, but the precise mode
of action is still not clear. We investigated the effects of vitamin K-2 o
n apoptosis of human osteoblasts. Human osteoblastic cell line MG63 cells a
nd human primary osteoblast-like cells obtained from bone fragments in corr
ective surgery were used as human osteoblasts. Cells were cultured with or
without various concentrations of vitamin K-2 and tumor necrosis factor-alp
ha (TNF-alpha). We then determined the proliferative response, expression o
f Fas and Bcl-2-related proteins, and Fas-mediated apoptosis of these cells
induced by anti-Fas immunoglobulin M (IgM). In addition, the effect of vit
amin K-2 in osteoblast apoptosis induced by Z-Leu-Leu-Leu-aldehyde (LLL-CHO
), etoposide, or staurosporine was also examined. Human osteoblasts did not
show spontaneous apoptosis in culture, even in the presence of vitamin K-2
or TNF-alpha. Furthermore, proliferation of the cells was not influenced b
y vitamin K-2 or TNF-alpha. Fas was functionally expressed on human osteobl
asts, and the treatment with TNF-alpha significantly enhanced both Fas expr
ession and Fas-mediated apoptosis of osteoblasts. The addition of vitamin K
-2 to the culture resulted in a dose-dependent inhibition of functional Fas
expression on osteoblasts, in the presence or absence of TNF-alpha. Treatm
ent of human osteoblasts with vitamin K-2 clearly suppressed Bax expression
of the cells, although the expression of Bcl-2 was not influenced by vitam
in K-2. Fas ligand (FasL) cDNA transformants were cytotoxic against osteobl
asts, and the cytotoxicity was increased when osteoblasts were treated with
TNF-alpha. The addition of vitamin K-2 to osteoblasts significantly decrea
sed the cytotoxic effects of FasL cDNA transformants. Furthermore, apoptosi
s of human osteoblasts induced by LLL-CHO, etoposide, or staurosporine was
also clearly suppressed in vitamin K-2-treated osteoblasts. Our results sug
gest that vitamin K-2 inhibits apoptotic cell death of osteoblasts and main
tains the number of osteoblasts. These actions may explain the therapeutic
efficacy of vitamin K-2 in osteoporosis.