Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.

AIM: Human periodontal ligament (PDL) cells incur changes in morphology and express proteins in response to cyclic strain. However, it is not clear whether cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and if so, what mechanism(s) are responsible. The aim of the prese...

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Main Authors: Li Wang, Jinsong Pan, Tingle Wang, Meng Song, Wantao Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3794943?pdf=render
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author Li Wang
Jinsong Pan
Tingle Wang
Meng Song
Wantao Chen
author_facet Li Wang
Jinsong Pan
Tingle Wang
Meng Song
Wantao Chen
author_sort Li Wang
collection DOAJ
description AIM: Human periodontal ligament (PDL) cells incur changes in morphology and express proteins in response to cyclic strain. However, it is not clear whether cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and if so, what mechanism(s) are responsible. The aim of the present study was to elucidate the molecular mechanisms by which pathological levels of cyclic strain induce human PDL cell apoptosis. MATERIALS AND METHODS: Human PDL cells were obtained from healthy premolar tissue. After three to five passages in culture, the cells were subjected to 20% cyclic strain at a frequency of 0.1 Hz for 6 or 24 h using an FX-5000T system. Morphological changes of the cells were assessed by inverted phase-contrast microscopy, and apoptosis was detected by fluorescein isothiocyanate (FITC)-conjugated annexin V and propidium iodide staining followed by flow cytometry. Protein expression was evaluated by Western blot analysis. RESULTS: The number of apoptotic human PDL cells increased in a time-dependent manner in response to pathological cyclic strain. The stretched cells were oriented parallel to each another with their long axes perpendicular to the strain force vector. Cleaved caspase-3 and poly-ADP-ribose polymerase (PARP) protein levels increased in response to pathological cyclic strain over time, while Rho GDP dissociation inhibitor alpha (RhoGDIα) decreased. Furthermore, knock-down of RhoGDIα by targeted siRNA transfection increased stretch-induced apoptosis and upregulated cleaved caspase-3 and PARP protein levels. Inhibition of caspase-3 prevented stretch-induced apoptosis, but did not change RhoGDIα protein levels. CONCLUSION: The overall results suggest that pathological-level cyclic strain not only influenced morphology but also induced apoptosis in human PDL cells through the RhoGDIα/caspase-3/PARP pathway. Our findings provide novel insight into the mechanism of apoptosis induced by pathological cyclic strain in human PDL cells.
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spelling doaj.art-569715ef0f4c4e6abba38ae5820428af2022-12-21T22:59:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7597310.1371/journal.pone.0075973Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.Li WangJinsong PanTingle WangMeng SongWantao ChenAIM: Human periodontal ligament (PDL) cells incur changes in morphology and express proteins in response to cyclic strain. However, it is not clear whether cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and if so, what mechanism(s) are responsible. The aim of the present study was to elucidate the molecular mechanisms by which pathological levels of cyclic strain induce human PDL cell apoptosis. MATERIALS AND METHODS: Human PDL cells were obtained from healthy premolar tissue. After three to five passages in culture, the cells were subjected to 20% cyclic strain at a frequency of 0.1 Hz for 6 or 24 h using an FX-5000T system. Morphological changes of the cells were assessed by inverted phase-contrast microscopy, and apoptosis was detected by fluorescein isothiocyanate (FITC)-conjugated annexin V and propidium iodide staining followed by flow cytometry. Protein expression was evaluated by Western blot analysis. RESULTS: The number of apoptotic human PDL cells increased in a time-dependent manner in response to pathological cyclic strain. The stretched cells were oriented parallel to each another with their long axes perpendicular to the strain force vector. Cleaved caspase-3 and poly-ADP-ribose polymerase (PARP) protein levels increased in response to pathological cyclic strain over time, while Rho GDP dissociation inhibitor alpha (RhoGDIα) decreased. Furthermore, knock-down of RhoGDIα by targeted siRNA transfection increased stretch-induced apoptosis and upregulated cleaved caspase-3 and PARP protein levels. Inhibition of caspase-3 prevented stretch-induced apoptosis, but did not change RhoGDIα protein levels. CONCLUSION: The overall results suggest that pathological-level cyclic strain not only influenced morphology but also induced apoptosis in human PDL cells through the RhoGDIα/caspase-3/PARP pathway. Our findings provide novel insight into the mechanism of apoptosis induced by pathological cyclic strain in human PDL cells.http://europepmc.org/articles/PMC3794943?pdf=render
spellingShingle Li Wang
Jinsong Pan
Tingle Wang
Meng Song
Wantao Chen
Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
PLoS ONE
title Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
title_full Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
title_fullStr Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
title_full_unstemmed Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
title_short Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.
title_sort pathological cyclic strain induced apoptosis in human periodontal ligament cells through the rhogdiα caspase 3 parp pathway
url http://europepmc.org/articles/PMC3794943?pdf=render
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AT tinglewang pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT mengsong pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT wantaochen pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway