PARP阻害薬olaparibは骨芽細胞の分化を抑制する

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  • PARP inhibitor olaparib suppresses osteogenic differentiation in MC3T3-E1 cells.

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<p>Poly(ADP-ribosyl)ation (PARylation) is a reversible post-translational modification catalyzed by the poly (ADP-ribose) polymerase (PARP) family proteins. PARylation regulates many biological processes such as DNA repair, cell death, transcriptional regulation and differentiation. The function of PARP1 has been well-studied in cancer sciences. Recently, a PARP inhibitor, olaparib, was approved as an anti-cancer agent for treatment of breast and ovarian cancer possessing BRCA1/2 mutations. On the other hand, little is known about 　the relation of osteogenic differentiation and PARP1. In this study, we analyzed the effects of olaparib on osteogenic differentiation to elucidate the role of PARP1 in the process of osteogenic differentiation. </p><p>Pre-osteoblastic MC3T3-E1 cells were induced to differentiate into osteogenic lineage with or without olaparib treatment. Up-regulation of alkaline phosphatase (ALP) activities accompanied with osteogenic differentiation was suppressed by olaparib at an early stage after differentiation induction (at day 14). Furthermore, Alizarin red S staining at 21 days after differentiation induction revealed that calcium deposition was significantly reduced by olaparib treatment. These results suggested that olaparib suppressed osteogenic differentiation of MC3T3-E1 cells in an initial stage of differentiation.</p>

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