The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction

Shen,Yun; Pan,Yongchu; Guo,Shuyu; Sun,Lian; Zhang,Chi; Wang,Lin

doi:10.3892/mmr.2020.11006

The roles of mechanosensitive ion channels and associated downstream MAPK signaling pathways in PDLC mechanotransduction

Authors:
- Yun Shen
- Yongchu Pan
- Shuyu Guo
- Lian Sun
- Chi Zhang
- Lin Wang
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Affiliations: Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: February 27, 2020 https://doi.org/10.3892/mmr.2020.11006
Pages: 2113-2122
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate whether the cytoskeleton, the Piezo1 ion channel and the transient receptor potential cation channel subfamily V member 4 (TRPV4) ion channel are equally functional in the mechanotransduction of periodontal ligament cells (PDLCs) and to reveal the interplay of these mechanically sensitive ion channels (MSCs). Human PDLCs (hPDLCs) were pretreated with cytochalasin D (the inhibitor of actin polymerization), GsMTx4 (the antagonist of Piezo1) and GSK205 (the antagonist of TRPV4), and then subjected to periodic mechanical loading. The expression levels of macrophage colony stimulating factor (M‑CSF), receptor activator of NF‑κB ligand (RANKL) and cyclooxygenase‑2 (COX2) in hPDLCs were detected via western blotting. Osteoblast mineralization induction capacity of the hPDLCs was also studied and the mitogen‑activated protein kinase (MAPK) expression profile was determined via protein microarray. The expression of Piezo1 and TRPV4 in the PDLCs was significantly increased at 8 h after loading. These differences in expression were accompanied by increased expression of M‑CSF, RANKL and COX2. Compared with the control group, key PDLC biomarkers were suppressed after mechanical loading following treatment with the inhibitors of Piezo1 (GsMTx4) and TRPV4 (GSK205). The phosphorylated‑MAPK protein array showed differential biomarker profiles among all groups. The present study suggested that both MSCs and the cytoskeleton participated as mechanical sensors, and did so independently in hPDLC mechanotransduction. Furthermore, the Piezo1 ion channel may transmit mechanical signals via the ERK signaling pathway; however, the TRPV4 channel may function via alternative signaling pathways.

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