Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Li, Pan, Jinsong, Wang, Tingle, Song, Meng, Chen, Wantao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794943/
https://www.ncbi.nlm.nih.gov/pubmed/24130754
http://dx.doi.org/10.1371/journal.pone.0075973
_version_ 1782287297918533632
author Wang, Li
Pan, Jinsong
Wang, Tingle
Song, Meng
Chen, Wantao
author_facet Wang, Li
Pan, Jinsong
Wang, Tingle
Song, Meng
Chen, Wantao
author_sort Wang, Li
collection PubMed
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.
format Online
Article
Text
id pubmed-3794943
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37949432013-10-15 Pathological Cyclic Strain-Induced Apoptosis in Human Periodontal Ligament Cells through the RhoGDIα/Caspase-3/PARP Pathway Wang, Li Pan, Jinsong Wang, Tingle Song, Meng Chen, Wantao PLoS One Research Article 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. Public Library of Science 2013-10-10 /pmc/articles/PMC3794943/ /pubmed/24130754 http://dx.doi.org/10.1371/journal.pone.0075973 Text en © 2013 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Li
Pan, Jinsong
Wang, Tingle
Song, Meng
Chen, Wantao
Pathological Cyclic Strain-Induced Apoptosis in Human Periodontal Ligament Cells through the RhoGDIα/Caspase-3/PARP Pathway
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794943/
https://www.ncbi.nlm.nih.gov/pubmed/24130754
http://dx.doi.org/10.1371/journal.pone.0075973
work_keys_str_mv AT wangli pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT panjinsong pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT wangtingle pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT songmeng pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway
AT chenwantao pathologicalcyclicstraininducedapoptosisinhumanperiodontalligamentcellsthroughtherhogdiacaspase3parppathway