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

Autor: Yongchu Pan, Lin Wang, Chi Zhang, Yun Shen, Shuyu Guo, Lian Sun
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
MAPK/ERK pathway
Cancer Research
Spider Venoms
Mechanotransduction
Cellular
Biochemistry
Ion Channels
Mice
0302 clinical medicine
Phosphorylation
Mechanotransduction
Child
mitogen-activated protein kinase pathway
Cells
Cultured
Mice
Inbred BALB C
biology
Chemistry
Articles
Piezo1
Cell biology
periodontal ligament cells
Oncology
RANKL
030220 oncology & carcinogenesis
Intercellular Signaling Peptides and Proteins
Molecular Medicine
Female
Mechanosensitive channels
transient receptor potential cation channel subfamily V member 4
Signal transduction
TRPV4
Cytochalasin D
Adolescent
MAP Kinase Signaling System
Periodontal Ligament
Protein Array Analysis
TRPV Cation Channels
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Genetics
Animals
Humans
Molecular Biology
Ion channel
mechanotransduction
Osteoblasts
Macrophage Colony-Stimulating Factor
RANK Ligand
PIEZO1
030104 developmental biology
Cyclooxygenase 2
biology.protein
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: 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.
Databáze: OpenAIRE
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