TAK-778 stimulates osteogenesis activity of alveolar bone-derived osteoblasts

Life Sciences 2007 (2007) Proc Life Sciences, PC587

Poster Communications: TAK-778 stimulates osteogenesis activity of alveolar bone-derived osteoblasts

L. S. Bellesini1, M. M. Beloti3, G. E. Crippa2, A. L. Rosa2

1. Department of Pharmacology, School of Medicine of Ribeirao Preto , University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. 2. Department of Oral and Maxillofacial Surgery, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. 3. Division of Oral Histology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.

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The aim of this study was to investigate the effect of TAK-778 on human osteoblasts derived from alveolar bone. Primary cells were obtained by enzimatic digestion of human alveolar bone fragments and cultured in osteogenic medium. First passage cells were cultured in 24-well culture plates (2 x 104 cells/well) or in culture flasks (8 x 104 cells/flask) in osteogenic medium containing TAK-778 (10-5 M) or vehicle. At days 7, 14 and 21, cell proliferation and viability, total protein content and alkaline phosphatase (ALP) activity were evaluated. Bone-like formation was evaluated at day 21. Quantitative polymerase chain reaction (RealTime-PCR) to investigate ALP, osteopontin (OP) and Cbfa1 gene expression was performed at day 7. All experiments were done in quintuplicate with exception of gene expression that was carried out in triplicate. Data were compared by ANOVA or Mann Whitney test. TAK-778 did not affect cell viability (p>0.05). Cell proliferation was reduced by TAK-778 at 14 and 21 days (p< 0.05). ALP activity, total protein content and bone-like nodule formation were increased by TAK-778 (p< 0.05). Expression of OP and ALP genes were up-regulated by TAK-778 (p< 0.05), while Cbfa1 gene was down-regulated (p< 0.05). TAK-778 enhanced key parameters of osteoblast differentiation including reduced cell proliferation, increased both ALP activity and bone-like formation and up-regulated the expression of OP and ALP genes. It means that TAK-778 could be a useful drug to enhance new bone formation in clinical situations that require rapid restoration of physiologic function.



Where applicable, experiments conform with Society ethical requirements.

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