TY - JOUR
T1 - Mechanotransduction of Ultrasound is Frequency Dependent Below the Cavitation Threshold
AU - Louw, Tobias M.
AU - Budhiraja, Gaurav
AU - Viljoen, Hendrik J.
AU - Subramanian, Anuradha
N1 - Funding Information:
This work was s upported, in part, by American Recovery and Reinvestment Act of 2009 Research Grant 1R21RR024437-01A1 from the Department of Health and Human Services .
PY - 2013/7
Y1 - 2013/7
N2 - This study provides evidence that low-intensity ultrasound directly affects nuclear processes, and the magnitude of the effect varies with frequency. In particular, we show that the transcriptional induction of first load-inducible genes, which is independent of new protein synthesis, is frequency dependent. Bovine chondrocytes were exposed to low-intensity (below the cavitational threshold) ultrasound at 2, 5 and 8 MHz. Ultrasound elevated the expression of early response genes c-Fos, c-Jun and c-Myc, maximized at 5 MHz. The phosphorylated ERK inhibitor PD98059 abrogated any increase in c-series gene expression, suggesting that signaling occurs via the MAPPK/ERK pathway. However, phosphorylated ERK levels did not change with ultrasound frequency, indicating that processes downstream of ERK phosphorylation (such as nuclear transport and chromatin reorganization) respond to ultrasound with frequency dependence. A quantitative, biphasic mathematical model based on Biot theory predicted that cytoplasmic and nuclear stress is maximized at 5.2 ± 0.8 MHz for a chondrocyte, confirming experimental measurements.
AB - This study provides evidence that low-intensity ultrasound directly affects nuclear processes, and the magnitude of the effect varies with frequency. In particular, we show that the transcriptional induction of first load-inducible genes, which is independent of new protein synthesis, is frequency dependent. Bovine chondrocytes were exposed to low-intensity (below the cavitational threshold) ultrasound at 2, 5 and 8 MHz. Ultrasound elevated the expression of early response genes c-Fos, c-Jun and c-Myc, maximized at 5 MHz. The phosphorylated ERK inhibitor PD98059 abrogated any increase in c-series gene expression, suggesting that signaling occurs via the MAPPK/ERK pathway. However, phosphorylated ERK levels did not change with ultrasound frequency, indicating that processes downstream of ERK phosphorylation (such as nuclear transport and chromatin reorganization) respond to ultrasound with frequency dependence. A quantitative, biphasic mathematical model based on Biot theory predicted that cytoplasmic and nuclear stress is maximized at 5.2 ± 0.8 MHz for a chondrocyte, confirming experimental measurements.
KW - Biphasic mathematical model
KW - Cell biomechanics
KW - Load-inducible genes
KW - Low-intensity ultrasound
KW - MAPPK/ERK
KW - Resonance
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U2 - 10.1016/j.ultrasmedbio.2013.01.015
DO - 10.1016/j.ultrasmedbio.2013.01.015
M3 - Article
C2 - 23562015
AN - SCOPUS:84878667723
SN - 0301-5629
VL - 39
SP - 1303
EP - 1319
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 7
ER -