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• W2105452967 abstract "The A2B adenosine receptor (A2B AR), activated in response to high levels of endogenous adenosine, is the major AR subtype involved in mesenchymal stem cell (MSC) differentiation to osteoblasts and bone formation. For this reason, targeting of A2B AR with selective allosteric modulators may represent a promising pharmacological approach to the treatment of bone diseases. Herein, we report the characterization of a 3-keto-indole derivative, 2-(1-benzyl-1H-indol-3-yl)-2-oxo-N-phenylacetamide (KI-7), as A2B AR positive allosteric modulator in MSCs, demonstrating that this compound is able to potentiate the effects of either adenosine and synthetic orthosteric A2B AR agonists in mediating osteoblast differentiation in vitro. In detail, we observed that MSC treatment with KI-7 determined an increase in the expression of osteoblast-related genes (Runx2 and osterix) and osteoblast marker proteins (phosphatase alkaline and osteocalcin), associated with a stimulation of osteoblast mineralization. In the early phase of differentiation programme, KI-7 significantly potentiated physiological and A2B AR agonist-mediated down-regulation of IL-6 release. Conversely, during the late stage of differentiation, when most of the cells have an osteoblast phenotype, KI-7 caused a sustained raise in IL-6 levels and an improvement in osteoblast viability. These data suggest that a positive allosteric modulation of A2B AR not only favours MSC commitment to osteoblasts, but also ensures a greater survival of mature osteoblasts. Our study paves the way for a therapeutic use of selective positive allosteric modulators of A2B AR in the control of osteoblast differentiation, bone formation and fracture repair." @default.
• W2105452967 created "2016-06-24" @default.
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• W2105452967 date "2014-12-01" @default.
• W2105452967 modified "2023-10-18" @default.
• W2105452967 title "Osteoblast differentiation and survival: A role for A2B adenosine receptor allosteric modulators" @default.
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• W2105452967 doi "https://doi.org/10.1016/j.bbamcr.2014.09.013" @default.
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• W2105452967 hasPublicationYear "2014" @default.
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