-
[show abstract]
[hide abstract]
ABSTRACT: Alkylphenols are endocrine disruptors that show estrogen-like effects in various wildlife species. However, little information is available about the action of these chemicals on bone metabolism. We investigated the effects of alkylphenols, such as nonylphenol (NP) and octylphenol (OP), on the formation of bone using several culture systems for osteoclasts and osteoblasts, as well as in vivo experiments. NP and OP dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) in cocultures of mouse spleen cells or mouse bone marrow cells with ST2 cells. However, beta-estradiol at 10(-9)M to 10(-6)M did not affect this process. In contrast, neither compound affected the proliferation and differentiation of rat calvarial osteoblast-like cells (ROB cells). When NP or OP (0.1mg/kg body weight) was administered subcutaneously to pregnant mice at 10 days, 12 days and 14 days post-coitus, fetuses at 17.5 days post-coitus showed stimulation of sternebrae bone calcification. Our findings suggest that alkylphenols have critical effects on the formation of bone by non-estrogenic effects.
Toxicology Letters 07/2008; 181(1):13-8. · 3.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tributyltin is ubiquitous in the environment and an endocrine disruptor for many wildlife species. However, minimal information is available regarding the effect of this chemical on bone formation. When tributyltin chloride (TBT) (1mg/kg body weight) was administered subcutaneously to pregnant mice at 10, 12, and 14 days post coitus (dpc), fetuses at 17.5 days post coitus revealed the inhibition of calcification of supraoccipital bone. In contrast, 1mg/kg body weight monobutyltin trichloride (MBT) did not affect the fetal skeleton. Therefore, we examined the effects of TBT and its metabolites (dibutyltin dichloride, DBT, and MBT) on bone metabolism using rat calvarial osteoblast-like cells (ROB cells). The viability of ROB cells was not affected by the exposure of the cells to 10(-10) to 10(-7)M TBT. However, TBT reduced the activity of alkaline phosphatase (ALPase) and the rate of deposition of calcium of ROB cells. In addition, the expression levels of mRNA for ALPase and osteocalcin, which are markers of osteoblastic differentiation, were depressed by the treatment with TBT. TBT inhibited ALPase activity and the deposition of calcium to a greater extent than did DBT. MBT had no effect on the osteoblast differentiation of ROB cells. Tributyltin is known to inhibit the activity of aromatase. However, the aromatase inhibitor aminoglutethimide did not reproduce the inhibitory effects of TBT on osteoblast differentiation. Our findings indicate that TBT might have critical effects on the formation of bone both in vivo and in vitro although its action mechanism is not clarified.
Biochemical Pharmacology 09/2004; 68(4):739-46. · 4.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It is possible that the flavonoids that are found in many foods might have a protective effect against osteoclastic activity. However, little information is available about the effects of flavonoids on osteoblastogenesis. Therefore, we investigated the effects of quercetin, a flavonoid, on the metabolism of rat calvarial osteoblast-like cells (ROB cells) in culture. The proliferation of cells was markedly inhibited upon exposure of cells to quercetin at 5 x 10(-6) to 1 x 10(-5) M. Quercetin at 1 x 10(-5) M did not induce apoptosis in ROB cells but arrested cells at the G1 phase of the cell cycle. In addition, quercetin stimulated the expression of mRNA for p21(waf1/cip1), which inhibits the activity of cyclin-dependent kinases, and inhibited the phosphorylation of histone H1. Furthermore, after cells had ceased to proliferate, quercetin reduced the activity of alkaline phosphatase, the level of expression of mRNA for osteocalcin, the rate of deposition of Ca(2+), and the formation of mineralized nodules, all of which are markers of osteoblast differentiation. These findings indicate that quercetin inhibits the proliferation, differentiation, and mineralization of osteoblastic cells.
European Journal of Pharmacology 03/2004; 485(1-3):89-96. · 2.52 Impact Factor
