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Sound Waves Induce Neural Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells via Ryanodine Receptor-Induced Calcium Release and Pyk2 Activation

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Abstract

Mesenchymal stem cells (MSCs) have shown considerable promise as an adaptable cell source for use in tissue engineering and other therapeutic applications. The aims of this study were to develop methods to test the hypothesis that human MSCs could be differentiated using sound wave stimulation alone and to find the underlying mechanism. Human bone marrow (hBM)-MSCs were stimulated with sound waves (1 kHz, 81 dB) for 7 days and the expression of neural markers were analyzed. Sound waves induced neural differentiation of hBM-MSC at 1 kHz and 81 dB but not at 1 kHz and 100 dB. To determine the signaling pathways involved in the neural differentiation of hBM-MSCs by sound wave stimulation, we examined the Pyk2 and CREB phosphorylation. Sound wave induced an increase in the phosphorylation of Pyk2 and CREB at 45 min and 90 min, respectively, in hBM-MSCs. To find out the upstream activator of Pyk2, we examined the intracellular calcium source that was released by sound wave stimulation. When we used ryanodine as a ryanodine receptor antagonist, sound wave-induced calcium release was suppressed. Moreover, pre-treatment with a Pyk2 inhibitor, PF431396, prevented the phosphorylation of Pyk2 and suppressed sound wave-induced neural differentiation in hBM-MSCs. These results suggest that specific sound wave stimulation could be used as a neural differentiation inducer of hBM-MSCs.

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Acknowledgments

This work was supported by the Pioneer Research Program of the National Research Foundation of Korea and was funded by the Ministry of Education, Science, and Technology (NRF-2009-0082941). This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (No. HI13C0540).

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    1. Department of Biomedical Engineering, Dongguk University, Biomedi-Campus, Sangyoung-Bio, Donggul-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea

      Yura Choi, Jong Seob Jeong, Jung-Keug Park & Jongpil Kim

    2. Dongguk University Research Institute of Bio-Medi Integration, Biomedi-Campus, Sangyoung-Bio, Dongguk-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea

      Jeong-Eun Park & Songhee Jeon

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    1. Yura Choi
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    Correspondence to Songhee Jeon.

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    Yura Choi and Jeong-Eun Park contributed equally to this work.

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    Choi, Y., Park, JE., Jeong, J.S. et al. Sound Waves Induce Neural Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells via Ryanodine Receptor-Induced Calcium Release and Pyk2 Activation. Appl Biochem Biotechnol 180, 682–694 (2016). https://doi.org/10.1007/s12010-016-2124-6

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