Mechanotransduction pathways regulating YAP nuclear translocation under Yoda1 and vibration in osteocytes

Chun-Yu Lin; Amel Sassi; Yuning Wu; Kimberly Seaman; Wentian Tang; Xin Song; Raphael Bienenstock; Hiroki Yokota; Yu Sun; Fei Geng; Liyun Wang; Lidan You

doi:10.1016/j.bone.2024.117283

Mechanotransduction pathways regulating YAP nuclear translocation under Yoda1 and vibration in osteocytes

Bone. 2024 Oct 14:117283. doi: 10.1016/j.bone.2024.117283. Online ahead of print.

Authors

Chun-Yu Lin¹, Amel Sassi², Yuning Wu³, Kimberly Seaman⁴, Wentian Tang⁵, Xin Song⁶, Raphael Bienenstock⁷, Hiroki Yokota⁸, Yu Sun⁹, Fei Geng¹⁰, Liyun Wang¹¹, Lidan You¹²

Affiliations

¹ Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada. Electronic address: delphine.lin@mail.utoronto.ca.
² Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada. Electronic address: amel.sassi@mail.utoronto.ca.
³ W Booth School of Engineering Practice and Technology, McMaster University, Hamilton, ON L8S 4L7, Canada. Electronic address: wuy198@mcmaster.ca.
⁴ Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada. Electronic address: kimberly.seaman@utoronto.ca.
⁵ Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada. Electronic address: wentian.tang@mail.utoronto.ca.
⁶ Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada. Electronic address: suzie.song@mail.utoronto.ca.
⁷ Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
⁸ Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA. Electronic address: hyokota@iupui.edu.
⁹ Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada. Electronic address: sun@mie.utoronto.ca.
¹⁰ W Booth School of Engineering Practice and Technology, McMaster University, Hamilton, ON L8S 4L7, Canada. Electronic address: gengf@mcmaster.ca.
¹¹ Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address: lywang@udel.edu.
¹² Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada; Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada; Mechanical and Materials Engineering, Queens University, Kingston, ON K7L3N6, Canada. Electronic address: you.lidan@queensu.ca.

PMID: 39413946
DOI: 10.1016/j.bone.2024.117283

Abstract

Yes-associated protein (YAP) is a mechanosensitive protein crucial for bone remodeling. Although research has identified pathways and components involved in YAP regulation, the precise mechanisms of its localization during Piezo1 activation or vibration remain unclear. Piezo1, a mechanosensitive ion channel, allows calcium ions to flow into cells upon activation. Recent studies suggest that combining Yoda1, a Piezo1 activator, with low-magnitude high-frequency (LMHF) vibration (>30 Hz, <1 g acceleration) enhances YAP nuclear translocation. This combination potentially improves the mechanoresponse and therapeutic efficacy of LMHF vibration in bone cells. This study aims to elucidate how Yoda1 and LMHF vibration regulate mechanosensitive structures and pathways, leading to YAP nuclear translocation in MLO-Y4 osteocyte like cells. We investigated the roles of the cytoskeleton and nuclear envelope (NE) in YAP activation under combined LMHF vibration and Yoda1 treatments. Additionally, we analyzed differentially expressed genes (DEGs) in MLO-Y4 cells subjected to these treatments and in Piezo1 knockdown MLO-Y4 cells exposed to vibration. Our findings indicated that increased YAP nuclear translocation with combined treatment may result from the distinct effects of Yoda1 and vibration. Specifically, Yoda1 influenced YAP through mechanisms involving actin and NE dynamics, while LMHF vibration may modulate YAP via the interleukin 6 (IL6)/signal transducer and activator of transcription 3 (STAT3) axis. This study provides new insights and potential therapeutic targets for osteocyte-related pathologies.

Keywords: Mechanotransduction; Nuclear envelope; Osteocytes; Piezo1; Stat3; Vibration; Yap.