title: Sound Waves Induce Neural Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells via Ryanodine Receptor-Induced Calcium Release and Pyk2 Activation.
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.
authors.affiliation: Department of Biomedical Engineering, Dongguk University, Biomedi-Campus, Sangyoung-Bio, Donggul-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Yura
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Dongguk University Research Institute of Bio-Medi Integration, Biomedi-Campus, Sangyoung-Bio, Dongguk-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Dongguk University, Biomedi-Campus, Sangyoung-Bio, Donggul-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Jong Seob
authors.initials: JS
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Engineering, Dongguk University, Biomedi-Campus, Sangyoung-Bio, Donggul-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Jung-Keug
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Dongguk University, Biomedi-Campus, Sangyoung-Bio, Donggul-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.
authors.forename: Jongpil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Dongguk University Research Institute of Bio-Medi Integration, Biomedi-Campus, Sangyoung-Bio, Dongguk-ro 32, Goyang-si, Gyeonggi-do, 10326, Republic of Korea. jsong0304@dongguk.edu.
authors.forename: Songhee
authors.initials: S
authors.lastname: Jeon
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013016:Sound
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D019837:Ryanodine Receptor Calcium Release Channel; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D051418:Focal Adhesion Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D009543:Nifedipine; D002118:Calcium
keywords: CREB; Mesenchymal stem cells; Neural differentiation; Pyk2; Sound waves