TAK-778 enhances osteoblast differentiation of human bone marrow cells via an estrogen-receptor-dependent pathway.
TAK-778, a derivative of ipriflavone, has been shown to induce bone growth in in vitro and in vivo models. However, there are no studies evaluating by which mechanism TAK-778 exerts its effect. Considering the evidences that its precursors act via classical estrogen-receptor (ER)-mediated signaling, in the present study, we tested the hypothesis that TAK-778 induces osteogenesis in human bone marrow cell culture via an ER-dependent pathway. Cells were cultured in 24-well culture plates at a cell density of 2 x 10(4) cells/well in culture medium containing: TAK-778 (10(-5) M), Tamoxifen (10(-5) M), TAK-778 (10(-5) M) + Tamoxifen (10(-5) M), and vehicle. During the culture period, cells were incubated at 37 degrees C in a humidified atmosphere of 5% CO(2) and 95% air. At 7, 14, and 21 days, cell proliferation, cell viability, total protein content, alkaline phosphatase (ALP) activity, and bone-like formation were evaluated. Data were compared by two-way ANOVA and Duncan's multiple range test. TAK-778 did not affect cell viability. Cell number was reduced by TAK-778. Total protein content, ALP activity, and bone-like formation were increased by TAK-778. In general, Tamoxifen did not have any effect on cell behavior. However, when cells were cultured in medium containing both TAK-778 and Tamoxifen, the effect of TAK-778 on osteoblast differentiation was inhibited. The present results show that TAK-778 enhances osteoblast differentiation in human bone marrow cell culture, at least in part, via an ER-dependent pathway, since its effect was inhibited by Tamoxifen, a well-known estrogen receptor antagonist.
Department of Oral and Maxillofacial Surgery, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Brazil. adalrosa@forp.usp.br
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D001582:Benzothiepins / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology
D001582:Benzothiepins; D011506:Proteins; D011960:Receptors, Estrogen; C120450:TAK 778; D013629:Tamoxifen