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Inhibition of CK2 binding to BMPRIa induces C2C12 differentiation into osteoblasts and adipocytes

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Journal of Cell Communication and Signaling Aims and scope

Abstract

BMP2 is a growth factor that regulates the cell fate of mesenchymal stem cells into osteoblast and adipocytes. However, the detailed signaling pathways and mechanism are unknown. We previously reported a new interaction of Casein kinase II (CK2) with the BMP receptor type-Ia (BMPRIa) and demonstrated using mimetic peptides CK2.1, CK2.2 and CK2.3 that the release of CK2 from BMPRIa activates Smad signaling and osteogenesis. Previously, we showed that mutation of these CK2 sites on BMPRIa (MCK2.1 (476S-A), MCK2.2 (324S-A) and MCK2.3 (214S-A)) induced osteogenesis. However, one mutant MCK2.1 induced osteogenesis similar to overexpression of wild type BMPRIa, suggesting that the effect of this mutant on mineralization was due to overexpression. In this paper we investigated the signaling pathways involved in the CK2-BMPRIa mediated osteogenesis and identified a new signaling pathway activating adipogenesis dependent on the BMPRIa and CK2 association. Further the mechanism for adipogenesis and osteogenesis is specific to the CK2 interaction site on BMPRIa. In detail our data show that overexpression of MCK2.2 induced osteogenesis was dependent on Caveolin-1 (Cav1) and the activation of the Smad and mTor pathways, while overexpression of MCK2.3 induced osteogenesis was independent of Caveolin-1 without activation of Smad pathway. However, MCK2.3 induced osteogenesis via the MEK pathway. The adipogenesis induced by the overexpression of MCK2.2 in C2C12 cells was dependent on the p38 and ERK pathways as well as Caveolin-1. These data suggest that signaling through BMPRIa used two different signaling pathways to induce osteogenesis dependent on CK2. Additionally the data supports a signaling pathway initiated in caveolae and one outside of caveolae to induce mineralization. Moreover, they reveal the signaling pathway of BMPRIa mediated adipogenesis.

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Authors and Affiliations

  1. Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA

    Oleksandra Moseychuk, Hemanth Akkiraju, Joyita Dutta, Alex D’Angelo, Beth Bragdon, Randall L. Duncan & Anja Nohe

  2. Department of Biology, University of Delaware, Newark, DE, 19716, USA

    Anja Nohe

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  1. Oleksandra Moseychuk
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  2. Hemanth Akkiraju
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  3. Joyita Dutta
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  4. Alex D’Angelo
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  6. Randall L. Duncan
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  7. Anja Nohe
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Correspondence to Anja Nohe.

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Moseychuk, O., Akkiraju, H., Dutta, J. et al. Inhibition of CK2 binding to BMPRIa induces C2C12 differentiation into osteoblasts and adipocytes. J. Cell Commun. Signal. 7, 265–278 (2013). https://doi.org/10.1007/s12079-013-0199-1

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  • DOI: https://doi.org/10.1007/s12079-013-0199-1

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