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Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase
Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associ...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806876/ https://www.ncbi.nlm.nih.gov/pubmed/34024253 http://dx.doi.org/10.1080/21655979.2021.1928930 |
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author | Liu, Di Du, Juan Sun, Jing Li, Minqi |
author_facet | Liu, Di Du, Juan Sun, Jing Li, Minqi |
author_sort | Liu, Di |
collection | PubMed |
description | Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associated with the activation of MAPK. Parathyroid hormone-related protein (PTHrP) can block the activity of MAPK by regulating the levels of MAPK phosphatase 1 (MKP1). Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Herein, alendronate sodium salt trihydrate (nitrogen-containing BP, FOS) and HPdLFs were co-cultured for 24 h, 48 h, and 72 h, and the levels of ROS and apoptosis were determined, respectively. After 48 h co-culture, FOS significantly increased the levels of ROS and apoptosis, and high phosphorylation levels of p38, ERK1/2 and p66(Shc) were found in this study. However, the inhibitors of p38 and ERK1/2 significantly reduced the apoptosis of HPdLFs. Interestingly, PTHrP pre-treatment significantly reduced the phosphorylation levels of p38, ERK1/2, and p66(Shc). More importantly, MKP1 inhibitor sanguinarine inhibited the dephosphorylation levels of p38, ERK1/2, and p66(Shc) caused by PTHrP. Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase. |
format | Online Article Text |
id | pubmed-8806876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-88068762022-02-02 Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase Liu, Di Du, Juan Sun, Jing Li, Minqi Bioengineered Research Paper Massive production of reactive oxygen species (ROS) in human periodontal ligament fibroblasts (HPdLFs) by nitrogen-containing bisphosphonates (BPs) is the main factor causing BP-related osteonecrosis of the jaw. Further, oxidative stress and apoptosis of fibroblasts induced by ROS are closely associated with the activation of MAPK. Parathyroid hormone-related protein (PTHrP) can block the activity of MAPK by regulating the levels of MAPK phosphatase 1 (MKP1). Therefore, it is speculated that PTHrP can inhibit the apoptosis of HPdLFs caused by nitrogen-containing BP via regulating the expression levels of MKP1. Herein, alendronate sodium salt trihydrate (nitrogen-containing BP, FOS) and HPdLFs were co-cultured for 24 h, 48 h, and 72 h, and the levels of ROS and apoptosis were determined, respectively. After 48 h co-culture, FOS significantly increased the levels of ROS and apoptosis, and high phosphorylation levels of p38, ERK1/2 and p66(Shc) were found in this study. However, the inhibitors of p38 and ERK1/2 significantly reduced the apoptosis of HPdLFs. Interestingly, PTHrP pre-treatment significantly reduced the phosphorylation levels of p38, ERK1/2, and p66(Shc). More importantly, MKP1 inhibitor sanguinarine inhibited the dephosphorylation levels of p38, ERK1/2, and p66(Shc) caused by PTHrP. Altogether, PTHrP can inhibit nitrogen-containing BP-induced apoptosis of HPdLFs by activating MKP1 phosphatase. Taylor & Francis 2021-05-23 /pmc/articles/PMC8806876/ /pubmed/34024253 http://dx.doi.org/10.1080/21655979.2021.1928930 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Liu, Di Du, Juan Sun, Jing Li, Minqi Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title | Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title_full | Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title_fullStr | Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title_full_unstemmed | Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title_short | Parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating MKP1 phosphatase |
title_sort | parathyroid hormone-related protein inhibits nitrogen-containing bisphosphonate-induced apoptosis of human periodontal ligament fibroblasts by activating mkp1 phosphatase |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806876/ https://www.ncbi.nlm.nih.gov/pubmed/34024253 http://dx.doi.org/10.1080/21655979.2021.1928930 |
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