title: The potential role of transient receptor potential type A1 as a mechanoreceptor in human periodontal ligament cells.
abstract: Transient receptor potential type A1 (TRPA1) is reported to be a Ca(2+) -permeable channel and is activated by cold temperatures and mechanical stimuli in the hair cells and in dorsal root ganglion. Using a DNA microarray, we found that TRPA1 was significantly up-regulated in human periodontal ligament (hPDL) cells 2 d after intermittent mechanical stimulation (iMS) loading compared with unloaded cells. Although hPDL cells are known to respond to mechanical stimulation induced by occlusal force, little is known about the expression and functional role of TRPA1 in these cells. Therefore, we investigated the effects of iMS on TRPA1 expression and its signaling pathway in hPDL cells. Intermittent mechanical stimulation loading up-regulated TRPA1 expression in hPDL cells in a time-dependent manner, but had no effect on other mechanoreceptors. Furthermore, iMS significantly increased the phosphorylation of mitogen-activated protein kinases (MAPKs), especially extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, and the expression of C-C chemokine ligand 2 (CCL2). Transient receptor potential type A1 agonists also increased MAPK phosphorylation and the intracellular Ca(2+) concentration. By contrast, inhibition or silencing of TRPA1 partially suppressed iMS-induced MAPK phosphorylation. In summary, iMS during occlusion activates TRPA1 and MAPK signaling in periodontal ligament tissues, suggesting that TRPA1 regulates the mechanosensitivity of occlusal force via activation of MAPKs in hPDL cells.
authors.affiliation: Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsutsumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiya
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Fukawa
authors.forename: Mina
authors.initials: M
authors.lastname: Sasaki
authors.forename: Tetsuomi
authors.initials: T
authors.lastname: Nemoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujii
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Maeda
authors.forename: Koji
authors.initials: K
authors.lastname: Okabe
mesh_terms: D000704:Analysis of Variance; D001732:Bite Force; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D008465:Mechanoreceptors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010513:Periodontal Ligament / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; D020928:Mitogen-Activated Protein Kinases
keywords: mechanical stimulation; mitogen-activated protein kinase; occlusal traumatism; periodontal ligament; transient receptor potential type A1