Cargando…
Long non‐coding RNA AC018926 .2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway
Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLS...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392068/ https://www.ncbi.nlm.nih.gov/pubmed/36720715 http://dx.doi.org/10.1111/cpr.13411 |
_version_ | 1785082866981404672 |
---|---|
author | Qu, Hong‐Lei Sun, Li‐Juan Li, Xuan Liu, Fen Sun, Hai‐Hua He, Xiao‐Tao Gan, Dian Yin, Yuan Tian, Bei‐Min Chen, Fa‐Ming Wu, Rui‐Xin |
author_facet | Qu, Hong‐Lei Sun, Li‐Juan Li, Xuan Liu, Fen Sun, Hai‐Hua He, Xiao‐Tao Gan, Dian Yin, Yuan Tian, Bei‐Min Chen, Fa‐Ming Wu, Rui‐Xin |
author_sort | Qu, Hong‐Lei |
collection | PubMed |
description | Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non‐coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss‐of‐function studies illustrated that AC018926.2 was an important regulator in PA‐mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro‐osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients. |
format | Online Article Text |
id | pubmed-10392068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103920682023-08-02 Long non‐coding RNA AC018926 .2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway Qu, Hong‐Lei Sun, Li‐Juan Li, Xuan Liu, Fen Sun, Hai‐Hua He, Xiao‐Tao Gan, Dian Yin, Yuan Tian, Bei‐Min Chen, Fa‐Ming Wu, Rui‐Xin Cell Prolif Original Articles Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non‐coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss‐of‐function studies illustrated that AC018926.2 was an important regulator in PA‐mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro‐osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients. John Wiley and Sons Inc. 2023-01-31 /pmc/articles/PMC10392068/ /pubmed/36720715 http://dx.doi.org/10.1111/cpr.13411 Text en © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Qu, Hong‐Lei Sun, Li‐Juan Li, Xuan Liu, Fen Sun, Hai‐Hua He, Xiao‐Tao Gan, Dian Yin, Yuan Tian, Bei‐Min Chen, Fa‐Ming Wu, Rui‐Xin Long non‐coding RNA AC018926 .2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title |
Long non‐coding RNA AC018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title_full |
Long non‐coding RNA AC018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title_fullStr |
Long non‐coding RNA AC018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title_full_unstemmed |
Long non‐coding RNA AC018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title_short |
Long non‐coding RNA AC018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway |
title_sort | long non‐coding rna ac018926
.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the itga2/fak/akt pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392068/ https://www.ncbi.nlm.nih.gov/pubmed/36720715 http://dx.doi.org/10.1111/cpr.13411 |
work_keys_str_mv | AT quhonglei longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT sunlijuan longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT lixuan longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT liufen longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT sunhaihua longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT hexiaotao longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT gandian longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT yinyuan longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT tianbeimin longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT chenfaming longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway AT wuruixin longnoncodingrnaac0189262regulatespalmiticacidexposurecompromisedosteogenicpotentialofperiodontalligamentstemcellsviatheitga2fakaktpathway |